Analysis of Carbohydrates and Glycoconjugates by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry: an Update for 2011–2012

ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES BY MATRIX-ASSISTED LASER DESORPTION/IONIZATION MASS SPECTROMETRY: AN UPDATE FOR 2011–2012

David J. Harvey* Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, Oxford OX1 3QU, UK Received 19 June 2014; accepted 15 January 2015 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mas.21471

This review is the seventh update of the original article published text. As the review is designed to complement the earlier work, in 1999 on the application of MALDI mass spectrometry to the structural formulae, etc. that were presented earlier are not analysis of carbohydrates and glycoconjugates and brings repeated. However, a citation to the structure in the earlier work coverage of the literature to the end of 2012. General aspects is indicated by its number with a prefix (i.e., 1/x refers to such as theory of the MALDI process, matrices, derivatization, structure x in the first review and 2/x to structure x the second). MALDI imaging, and fragmentation are covered in the first part Books, general reviews, and review-type articles directly of the review and applications to various structural types concerned with, or including, MALDI analysis of carbohydrates constitute the remainder. The main groups of compound are and glycoconjugates to have been published during the review oligo- and poly-saccharides, glycoproteins, glycolipids, glyco- period are listed in Table 1. Reviews relating to more specific sides, and biopharmaceuticals. Much of this material is presented aspects of MALDI analysis are listed in the appropriate sections. in tabular form. Also discussed are medical and industrial applications of the technique, studies of enzyme reactions, and II. THEORY applications to chemical synthesis. # 2015 Wiley Periodicals, Inc. Mass Spec Rev Investigations into the mechanisms operating during MALDI Keywords: MALDI; carbohydrates; glycoproteins; glycolipids; ionization continue. Knochenmuss and Zhigilei (2012) have biopharmaceuticals pointed out that, although ion recombination is an important process in determining the number of ions observed, this reaction has received comparatively little attention. In their I. INTRODUCTION study, molecular dynamics simulations were used to investigate the process and a tunneling model was found to explain some of This review is a continuation of the seven earlier ones in this the observations. They propose that “tunneling recombination in series on the application of MALDI mass spectrometry to the the Marcus inverted region may be a major reason why MALDI analysis of carbohydrates and glycoconjugates (Harvey, 1999, is a viable analytical method by allowing ion formation to 2006, 2008, 2009, 2011a, 2012, 2015) and is intended to bring exceed ion loss on the time scale of the plume expansion.” the coverage of the literature to the end of 2012. It is hoped that Jaskolla and Karas (2011) have devised an experiment to this review is relatively comprehensive but this is becoming show that both of the postulated mechanisms for ion production increasingly difficult in view of the massively increasing number by protonation under MALDI conditions, the Lucky Survivor of papers and journals published each year and the splitting of and the gas-phase protonation models, exist together. The papers between the main text and “supplementary material.” experiment used the deuterated t-butyl ester of a-cyano-4- Some papers published in the review period will invariably have hydroxycinnamic acid (CHCA, 1/23) as the matrix. This been overlooked if the technique is not deemed sufficiently compound is stable under typical sample preparation conditions important to appear in the main text of an article. An excessive but generates deuterated reagent ions, including the deuterated use of acronyms and abbreviations, is another problem with and deuterium-free matrix acid, only upon laser irradiation. The modern scientific writing. A recent Editorial in Nature Methods generation of deuterated analyte ions proves the existence of the (Editorial, 2011) cautions against the excessive or inappropriate gas-phase protonation model and the detection of protonated use of acronyms, particularly for new experimental techniques analytes by application of deuterated matrix compounds without but cites MALDI as an example of the good and appropriate use acidic hydrogens proves the survival of analytes pre-charged of an acronym. from solution. The observed ratio of ions from the two ionization MALDI continues to be a major technique for the analysis processes depends on the applied experimental parameters as of carbohydrates; Figure 1 shows the year-by-year increase in well as the nature of the analyte and matrix. Increased laser papers reporting use of the technique for the period 1987–2012. fluences and lower matrix proton affinities favor gas-phase Slightly fewer papers than expected were found but this may protonation, whereas more protonation in solution leads to more relate, as mentioned above, to absence of MALDI in the main Lucky Survivors. Another feature of a MALDI ion source is the angle at Correspondence to: David J. Harvey, Department of Biochemistry, which the sample/matrix plume is emitted. To address this issue, Oxford Glycobiology Institute, University of Oxford, Oxford OX1 Liang et al. (2011b) have measured the high-resolution angular 3QU, UK. E-mail: [email protected] and velocity distributions for the neutral analytes, tryptophan,

Mass Spectrometry Reviews, 2015, 9999, 1–168 # 2015 by Wiley Periodicals, Inc. & HARVEY

FIGURE 1. Numbers of papers per year relating to the application of MALDI MS to the study of carbohydrates and glycoconjugates. and poly-tryptophan ionized with 2,4,6-trihydroxyacetophenone beginning of desorption when the surface temperature was high. (THAP, 1/44) using 355 nm laser desorption. The results This expansion resulted in a large velocity normal to the surface suggested that two separate mechanisms dominate the angular and a very narrow angular distribution. Before the end of and velocity distributions at the beginning and before the end of desorption, the surface temperature decreased and thermal desorption. A molecular jet-like isentropic (constant entropy) desorption at low vapor pressure was the dominant process. expansion was found to dominate the plume expansion at the Under these conditions, the velocities become small and the

TABLE 1. General reviews No. of Subject Notes Reference citations In situ pressure probe sampling and UV-MALDI (Gholipour et Plant cells 37 MS for profiling metabolites in living single cells al., 2012) Several techniques. MALDI (Ho & Reddy, Identification of pathogens 260 detection of lipid A etc. 2011) (Horn & Lipidomics in tissues, cells and subcellular General review, some 102 Chapman, compartments glycolipids 2012) High-resolution plant metabolomics: whole-cell (Kueger et al., Short general review 139 analysis to subcellular metabolite distributions 2012) (Oikawa & Metabolite analyses of single cells Small section on MALDI 88 Saito, 2012) Gold nanomaterials as a new tool for bioanalytical Applications to several (Pilolli et al., applications of laser desorption ionization mass 97 structural types 2012) spectrometry Short general review on characterization of mainly (Robinson et GAGs N-links, glycan arrays 224 acidic glycans al., 2012) Application of surface plasmon resonance for the Section on MALDI and in 201 (Safina, 2012) detection of carbohydrates and glycoconjugates combination with SPR A review of the progress in (Schiller et al., TLC/HPTLC with mass spectrometric detection 98 the last 5 years 2011) Thin-layer chromatography and mass spectrometry Several compound types - (Tuzimski, for the separation and detection of large and small 228 carbohydrates peptides etc. 2011) biomolecules Review of reactions (Urban et al., -on-a- performed on MALDI plates. 332 2011) Tables of applications Mainly N- and O-linked glycans. Most rearrangements (Wuhrer et al., Glycan rearrangements 51 associated with presence of a 2011) proton

2 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & angular distribution increases. Unlike the initial situation where in ambient MALDI plumes. A large number of nanoparticles much analyte is present in the plume, only a very small amounts were produced, with average particle diameters ranged from 40 of analyte are generated by thermal desorption. to 170 nm depending on the matrix and the laser fluence. CHCA The relationships between MALDI ion yield(s) as a and sinapinic acid also produced particles in the range of 10 to function of desorption alone and (or) ionization have been 30 nm, which was attributed to the direct ejection of clusters. investigated using two model systems. In the first model system, The work has relevance to ionization methods such as matrix- b-cyclodextrin (b-CD, 4/6), which could be directly desorbed, assisted laser desorption electrospray ionization (MALDESI) was analyzed with and without a silicon-based heat sink where it will be important to produce larger particulates to compound. The sink allowed heat to pass through but obstructed facilitate analyte transfer to the charged electrospray droplet. the flow of charge. In the second model system, substance P, Gas-phase basicities of several MALDI matrices have been which could not be desorbed, was analyzed under similar measured using an electrosonic spray ionization source. Mea- conditions. The ion yields from b-CD under either system of sured values were CHCA: 908.1 0.8, ferulic acid (1/41): heat conductivity were found to be similar, whereas the ion yield 863.8 8.0, 3-hydroxypicolinic acid (1): 876.3 10.2, sina- of the peptide with the heat sink was negligible. It was pinic acid: 867.4 1.4, and THAP 864.2 7.6 kJ/mol. Good concluded that compounds that are predominately cationized agreement was found between the experimentally measured and either in the gas phase or preformed in solution give an ion yield computationally predicted basicities except for CHCA for which that is not dependent upon the surface conditions, whereas the calculations resulted in a value of approximately 80 kJ/mol compounds that are not usually cationized are affected by the low. This discrepancy was attributed to a gas-phase rearrange- emission of electrons from the metal surface (Lourantos et al., ment of CHCA into the more stable heterocyclic aromatic 2011). isomer, 7-hydroxyquinoline-3-carboxylic acid (2) (Barylyuk Molecular dynamics simulations have been employed in an et al., 2012). Sodium cation affinities of the commonly used effort to understand analyte ejection from the matrix. Earlier MALDI matrices, nicotinic acid (1/20), quinoline (7/10), 3- calculations show that the ejected analyte molecules remain aminoquinoline (3-AQ, 1/24), 4-nitroaniline (3/3), picolinic acid solvated by the matrix molecules in the ablated plume, whereas (3/2), and 3-hydroxypicolinic acid have been determined by the experimental data show the presence of free analyte ions. guided ion beam tandem mass spectrometry, again with good The main idea of this work is that analyte molecule ejection may agreement with calculated values (Chinthaka & Rodgers, depend on the microscopic details of analyte interaction with the 2012). matrix. Intermolecular matrix–analyte interactions have been studied using 2,5-dihydroxybenzoic acid (DHB, 1/26) and OH amino acids using Chemistry at HARvard Molecular Mechanics (CHARMM) force field. Results show that a few analyte OH molecules, mainly lacking extra –COOH and –NH2 groups, can N free themselves from the matrix. Alanine was found to be the least attractive toward DHB (Nangia & Garrison, 2011). O Work with peptides using either IR-MALDI) with glycerol 1, 3-Hydroxypicolinic acid as the matrix or by ultraviolet MALDI with CHCA, sinapinic acid (SA, 1/48), or DHB has indicated that collisional activation during ion extraction and exothermicity in the gas-phase proton O transfer is unimportant as the driving forces for in-source decay (ISD) and post-source decay (PSD). This result suggests that the OH thermal energy acquired during photo-ablation is responsible for their occurrence. The proposed model explains why MALDI is HO N more successful for mass spectrometry of labile molecules than 2, 7-Hydroxyquinoline-3-carboxylic acid other desorption techniques that do not utilize a matrix (Bae et al., 2011). Energetics for substitution of hydrogen with sodium have III. INSTRUMENTATION been studied for THAP (Charkin et al., 2011). Calculations show that the first substitution of Na for H is slightly exothermic A MALDI-linear ion trap mass spectrometer for large biomolec- and, presumably, can occur spontaneously under common ular ion detection using radio frequency scanning has been conditions. Further substitutions are endothermic, but require described (Lu et al., 2011a). The RF circuit could be adjusted only a small amount of energy. Therefore, for relatively low from 300 to 10 kHz with a set of operation amplifiers. To trap the inputs of energy, successive substitutions for two, three, or more ions produced by MALDI, a high pressure of helium buffer gas hydroxyl H atoms are possible. In the system of glucose þ was employed to quench extra kinetic energy of the heavy ions þ CH3COONa þ THAP, in addition to the common [MþNa] and produced by MALDI. The successful detection of the singly [THAPþNa]þ ion-molecular complexes, multiple substituted charged secretory IgG-A ions indicated that the detectable mass positive ions of the [Glc-nHþ(n þ 1)Na]þ type where n ¼ 1–4 range of the instrument was at least 385,000. and [THAP-nHþ(n þ 1)Na]þ where n ¼ 1–3 are possible. An atmospheric pressure visible-wavelength MALDI in- Musapelo and Murray (2011) have used a scanning mobili- strument has been constructed with a frequency-doubled Nd: ty particle sizer combined with a light scattering aerodynamic YAG laser, which emits pulsed light at 532 nm, and combined particle sizer to measure the size of particles ejected from the with a commercial electrospray ionization Q-TOF mass spec- matrices DHB, 4-nitroaniline (3/3), CHCA, and sinapinic acid trometer. The dyes, neutral red (3), nuclear fast red (4),

Mass Spectrometry Reviews DOI 10.1002/mas 3 & HARVEY rhodamine B (5), rhodamine 6 G (6), rhodamine B isothiocyanate (7), and 5(6)-carboxytetramethyl-rhodamine N-succini- O midyl ester (8) which absorb green light were investigated as O matrices and compounds such as peptides, oligosaccharides, and N O synthetic polymers were successfully analyzed at atmospheric O 7/16 pressure. The trisaccharide, rafﬁnose ( ), was ionized with O O nuclear fast red (Sun, Findsen, & Isailovic, 2012).

H3C CH3 H3C N N ON Cl CH3 CH3 CH3 H N N N 2 8, 5(6)-Carboxytetramethyl-rhodamine N-succinimidyl ester H CH3

3, Neutral red A novel tandem MALDI-TOF/TOF mass spectrometer (3-Amino-7-dimethylamino-2-methylphenazine HCl) with a spiral ion trajectory, “SpiralTOF (STOF)(JEOL Ltd., Akishima, Tokyo),” a collision cell, and an offset parabolic reﬂectron has been used for tissue imaging. The features of this

O NH2 system are high precursor ion selectivity due to a 17-m flight path in the spiral flight tube and elimination of PSD ions. The OH acceleration energy was 20 keV, allowing high-energy collision- O induced dissociation experiments to be performed. Mass resolu- S tion was typically around 40,000. In the report by Shimma et al. O (2012), the instrument was used to profile lipids and glycolipids O OH ONa from mouse brain using the liquid matrix 3-aminoquinline/ 4, Nuclear fast red CHCA (3-AQ/CHCA). A pre-spotted MALDI plate, which overcomes the problem of the large crystal formation from DHB, has been developed by Ha et al. (2011a). A homogeneous matrix-coated surface without R a crystal structure was formed on a hydrophilic/hydrophobic patterned surface with 1700 mm spots using a piezoelectric device with 5760 1440 dpi resolution and a six channel piezoelectric 2 OH head that delivered 87 pl per 200 mm .Thetargetwasusedfor recording the MALDI spectra from beer and serum glycans. O

Cl A. Laserspray

H C N ONCHLaserspray ionization (LSI) is a related technique to MALDI 3 3 except that the spectra are multiply charged and resemble ESI spectra. Trimpin et al. (2012) suggest that the prompt and H C CH 3 3 delayed ionization reported for vacuum MALDI yielding 5, R = H, Rhodamine B predominantly singly charged ions are both fast processes 7, R = NCS, Rhodamine B isothiocyanate relative to those producing highly charged ions by LSI. The energy supplied to produce these charged clusters/droplets as well as their size and time available for desolvation are determining factors in the charge states of the ions observed. Furthermore, they propose that charged droplets/clusters may be a common link for ionization of non-volatile compounds by a OCH3 variety of MS ionization methods, including MALDI and LSI. O H3C CH3 IV. MATRICES

H A. General H3C N ON Cl Ropartz et al. (2011) have evaluated more than 40 matrices in an H attempt to ﬁnd the smallest set of MALDI matrices able to detect CH 3 chemically heterogeneous oligosaccharides. Homogeneity of analyte–matrix deposits was considered as a critical feature, 6, Rhodamine 6G especially since the ﬁnal objective was to fully automate the analyses. Matrix evaluation was performed by means of a

4 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & rigorous statistical approach and the use of a DHB/N,N- dimethylaniline (DMA, 9) ionic mixture was proposed as the O most generic matrix for rapid detection of a variety of carbohydrates including neutral, anionic, methylated, sulfated, OH and acetylated compounds. The selected matrices were then CN used to screen crude bacterial incubation media for the detection Cl of enzymatic degradation products. 12, 4-Chloro- -cyano H3C CH3 cinnamic acid (Cl-CCA) N A common problem with analysis of sialylated glycans by MALDI is the loss of sialic acid. Several methods have been employed to overcome this difficulty such as the use of laserspray (see below). Selman et al. (2012) have approached the problem by investigating various matrices and have found that Cl-CCA was advantageous for the 9 N N , , -Dimethylalinine analysis of both sialylated N-glycans and glycopeptides in negative-ion mode. Dried droplet preparations produced microcrystals with a homogeneous spatial distribution and B. Simple Matrices high shot-to-shot repeatability similar to those produced by Several CHCA-based matrices, including two newly synthe- CHCA. Detection sensitivity was better than with DHB for sized compounds, (E)-2-cyano-3-(naphthalen-2-yl) acrylic acid glycopeptides and for released glycans from fetuin, Cl-CCA (NpCCA, 10) and (2E)-3-(anthracen-9-yl)-2-cyanoprop-2-enoic gave lower intensity peaks for the mono-sialylated species acid (AnCCA, 11), and the recently developed 4-chloro-a- than did DHB, suggesting less sialic acid loss. Studies were cyanocinnamic acid (Cl-CCA, 12) matrices (Jaskolla, Lehmann, also made on permethylated glycans where again more & Karas, 2008) have been compared by measuring the signal-to- intense signals were observed for the larger glycans. noise ratios (S/N) of 47 analytes, mostly pharmaceuticals, using Reflectron-positive-ion mode analysis of 1-phenyl-3-methyl- 5/7 selected reaction monitoring (SRM) mode on a triple quadrupole 5-pyrazolone (PMP, )-labeled O-glycans ionized with Cl- instrument equipped with a vacuum MALDI source. AnCCA, CCA in reflectron-positive mode revealed more complete NpCCA, and Cl-CCA were found to offer better signal-to-noise profiles than with DHB or CHCA. ratios than CHCA, but Cl-CCA yielded the best results for 60% Liang et al. (2012a) have found that high yields of ! of the compounds tested. This matrix has also been reported to carbohydrate (maltopentaose ((Glc)5,1 4-linked) and polysac- facilitate the ionization of less basic peptides and has been used charides) ions with very low backgrounds can be obtained from to study glycation of whey proteins (Carulli et al., 2011). Proton frozen solutions. To prepare the samples, 1 mL of an aqueous affinities of these matrices were measured using the kinetic acetonitrile solution of the oligosaccharides and DHB was method and their relative values were found to be AnCCA > deposited onto the sample plate and then immediately sprayed 8 CHCA > NpCCA > Cl-CCA. This ordering is consistent with with low-temperature nitrogen to cool it to about 100 K. The the performance data (Porta et al., 2011). sample preparation chamber was then pumped down to a pressure of 1 106 Torr. The spectrum was recorded without O melting the sample by keeping the sample plate in thermal contact with a cold finger maintained at 1008 K. Spectra were compared with those prepared without freezing and a dramatic OH increase in ion yield and signal-to-noise ratio, together with a CN reduction in PSD ions was observed. Furthermore, the ion signal was long-lasting and the target showed enhanced homogeneity. CHCA and sinapinic acid showed similar enhancements in 10 , (E)-2-Cyano-3-(naphthalen- signal strength but ionic liquids (DHB þ pyridine and CHCA þ 2-yl)-acrylic acid (NpCCA) butylamine) did not. The frequently used dried-droplet preparation with DHB often results in a large variation in signal intensity and poor O shot-to-shot reproducibility. Nishikaze et al. (2012a) have investigated the crystals formed by the matrix using Raman OH spectrometry and found that they exist as two polymorphs. Using peptides and glycopeptides, the investigators found that CN the peptides were distributed in both types of crystals, whereas the glycopeptides distributed mainly to the Raman spectrum B, which is generated at the early stages of crystallization. Derivatization with pyrenebutyric acid hydrazide (6/21) gave a 11, (2E)-3-(Anthracen-9-yl) hydrophobic pyrene-containing derivative which caused the -2-cyanoprop-2-enoic acid glycopeptides to distribute among both types of crystal, increas- (AnCCA) ing the number of “sweet spots.” The authors advocate rendering

Mass Spectrometry Reviews DOI 10.1002/mas 5 & HARVEY the analyte as hydrophobic as possible for optimum signal molecular weight region by matrix-derived ions. Glucose (1/4) strength. was monitored in negative-ion mode by its [MþCl] ion and 13 A comparison of DHB, CHCA, and C70 fullerene for quantified with 1,2-[ C2]-glucose as the internal standard. detection of anthocyanins in wine and grapes has shown DHB to Because of the overlap of the peaks of [glucose þ 37Cl] and 13 35 be the best (Ivanova et al., 2011). C70 fullerene was unsuitable [glucose-1,2[ C2] þ Cl] at m/z 217.03, the ion intensity 35 13 37 because the higher laser energy needed for ionization caused ratios of [glucose þ Cl] and [glucose-1,2-[ C2] þ Cl] extensive fragmentation of the sugars leading to detection of the were monitored. A low detection limit of approximately 10 mM aglycone only. Fullerene substituted with two phenyl-C8F17 for glucose in 126 mM NaCl (a typical component in artificial groups (13) has also been reported as a matrix and was found to cerebrospinal fluid) was achieved without prior sample be particularly suitable for the analysis of mono- and small purification. oligosaccharides because of the absence of interfering matrix ions (Liu et al., 2012d). NH2 NH C8F17 2HCl C8F17

15, N-(1-Naphthyl)ethylenediamine dihydrochloride (NEDC)

The salt, N-(1-naphthyl)ethylenediamine dinitrate (NEDN), has been found to be a very good matrix for small molecules, including carbohydrates, with the production of very few matrix-associated ions in negative-ion mode. Carbohydrates formed [MþNO3] ions which, on analysis by PSD, yielded abundant diagnostic cross-ring fragment ions (Chen et al., 2012c). 2-Hydroxy-5-nitrobenzoic acid (16) also performed well in positive-ion mode but also yielded cross-ring fragments A new flavonoid matrix, with a chalcone structure (iso- in ISD as the result of hydrogen abstraction by the anion 0 0 liquiritigenin, 4,2 ,4 -trihydroxychalcone, 14), has been reported (Asakawa et al., 2012). to give superior performance for analysis of carbohydrates with lower laser power than the common matrices DHB and THAP. O OH The dried droplet method of target preparation gave the best performance. The matrix was claimed to produce higher homogeneity of crystallization on the target, a property that OH allowed automatic data acquisition, good quantitative behavior, good spectral quality in terms of resolution and signal-to-noise ratio, good salt tolerance, and sufficient fragmentation for it to O2N be used in LIFT-TOF/TOF MS. Spectra of maltohexaose and 16 cyclodextrins were shown (Yang et al., 2011d). , 2-Hydroxy-5-nitrobenzoic acid OH O C. Binary Matrices One use of binary matrices is to form small crystals in conditions where compounds such as DHB produce large crystals leading HO OH to a very inhomogeneous crystal surface. An example of this effect is the binary matrix 5-chloro-2-mercaptobenzothiazole 1/33 14, Iso-liquiritigenin, 4,2’,4’-trihydroxychalcone (CMBT, )/DHB which has been found to form homogeneous microcrystals, improving detection sensitivity of glyco- Low molecular weight fragments of fucoidan from the red peptides (Yu, Luo, & Yang, 2011). Another is a matrix formed seaweed, Fucus avanescens, are prone to in-source fragmenta- by addition of EDTA ammonium salt to CMBT which has tion and loss of sulfate groups when DHB or nor-harmane (1/35) produced an improvement in ion intensity for the di-phosphory- was used as matrices. However, Anastyuk et al. (2012c) lated and monophosphorylated lipid A from the bacterium have shown that these problems can be minimized by use of Shigella flexneri variant X in negative-ion mode (Casabuono arabinosazone as a matrix in negative-ion mode. et al., 2012). N-(1-naphthyl)ethylenediamine dihydrochloride (NEDC) A mixture of THAP and alkali metal cation-substituted (15) has been used as a matrix to measure the level of glucose in zeolites has been used to produce abundant ions from maltohex- rat brain microdialysates by MALDI-TOF MS in combination aose (Suzuki & Fujino, 2012). The ion that was formed with in vivo microdialysis (Chen et al., 2012d). The matrix had ([MþNa]þ, etc.) depended on the alkali metal bound to the high salt tolerance and showed little interference in the low surface of the zeolite.

6 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

D. Liquid Matrices The use of graphene and its derivatives is another approach for reducing background noise. Thus, spectra of small mole- An advantage of this type of matrix is that it tends to produce a cules, including nucleosides, nucleotides, fatty acids, amino much more homogeneous surface than a crystalline matrix, thus acids, and peptides have been obtained by the use of graphene producing a system that is much more appropriate for imaging flakes. Targets were prepared by pipetting a solution of the and quantitative work. Thus, ionic liquids consisting of sinapinic sample and flakes directly onto the target and irradiating them acid and nitrogen-containing compounds such as pyridine, with a nitrogen laser. Negative ions gave the best results triethylamine or trimethylamine have been shown to be benefi- þ ([MH] ions), although positive ions of the type [MþNa] cial with microfluidic sample deposition devices (Weidmann could also be obtained. The authors believed that the method et al., 2012). The resulting matrix surface was homogeneous and could be applied more generally to other types of compound (Lu the matrix did not cause clogging of the spotting device. et al., 2011b). Several other systems have been developed, such On the other hand, 3-AQ/CHCA, first reported by Kolli and as the nanoengineered micro gold shells introduced by Lee et al. Orlando (1996), has been found to concentrate hydrophilic (2012e). The gold shells gave a better limit of detection and a material into the center of the MALDI target during solvent higher signal-to-noise ratio than gold nanoparticles, which are (water) evaporation. Imaging analyses showed that oligosac- commonly used for laser desorption ionization (LDI)-TOF charides distributed to the center, whereas peptides tended to analysis of small molecules. concentrate nearer to the periphery. This “on-target separation” Another method for examination of small molecules is the effect was also applicable to glycoprotein digests such as that use of magnetic graphene/carbon nanotube composites reported from ribonuclease B and, thus, reduce the requirement for pre- by Shi, Meng, and Deng (2012). These compounds act both as MS cleanup (Sekiya, Taniguchi, & Tanaka, 2012). enrichment media and as MALDI matrices. They produced The use of ionic liquids added to the glycan solution has strong spectra and exhibited very high salt tolerance. A been used to alter the appearance of electrospray spectra by comparison of graphene, graphene oxide, and reduced graphene suppressing multiple charging and producing mainly singly oxide for analysis of flavonoids has been made by Liu et al. charged ions resembling a MALDI spectrum. Glycans ionized (2012a). Graphene oxide proved to be the best matrix with by cation or anion attachment and very little protonation or spectra recorded in negative-ion mode. Graphene and graphene deprotonation were observed (Chang et al., 2011a). oxide have also been used to ionize small molecules from A review of liquid matrices has been published by traditional Chinese medicinal herbs. The large surface area of Fukuyama (2011) (21 references). these matrices resulted in strong attachment of the analytes and avoided contamination of the ion source and vacuum system. E. Matrices for Small Molecules Low background noise made them ideal for examination of small molecules such as the flavonoids-type compounds such as Several investigators have reported matrices that produce few, if scutellarin (17) used in this study (Liu et al., 2011d). Graphene any matrix-derived ions and which are, therefore, appropriate oxide and aminated multi-walled carbon nanotubes in a double- for the analysis of small molecules such as monosaccharides and layer-based system have also been developed for the detection the subject has been reviewed (van Kampen et al., 2011) (123 of small molecules and mass spectrometric tissue imaging. The references), (Wang et al., 2011e) (210 references), and (Rainer, matrix exhibited a homogeneous surface with no sweet spots Qureshi, & Bonn, 2011) (971 references). One approach is to and produced minimal fragmentation (Kim et al., 2011e). use nanoparticles. Thus, Au@SiO2 core-shell nanoparticles with Hybrid films of poly(allylamine hydrochloride)-functionalized thick silica shells of 10–30 nm have been used to ionize several graphene oxide and gold nanoparticle (Kim & Min, 2012b) and types of small molecules such as polyethylene glycol (PEG), alternating multilayer films of graphene oxide and carbon antibiotics, and small carbohydrates (maltose) (Zhu et al., nanotubes (Kim & Min, 2012a) have also shown promise for the 2012b). Results compared favorably with MALDI ionization analysis of small molecules. from CHCA. Bare gold nanoparticles (AuNPs) have also been used as matrices for small molecules such as neutral steroids and OH OH carbohydrates (Lin & Tseng, 2011). Samples were prepared by O O deposition of the analyte onto the target, drying, and addition of O O the nanoparticles. The method, which produced [MþNa]þ ions, HO HO was reported to offer advantages over the dried droplet method OH by improving shot-to-shot reproducibility, increasing the ioniza- HO tion efficiency and reducing sample preparation time. HgTe OH O nanostructures mixed with ammonium citrate and NaCl have also shown promise for ionization of small carbohydrates such 17, Scutellarin as sucrose and cyclodextrins, and large molecules such as pullulans from the microorganism Aureobasidium pullulans, with molecular weights of approximately 5900 and 9600. The F. Matrices Producing Negative Ions from method was quantitative with detection limits in the low Neutral Glycans nanomolar range (Huang & Chang, 2012). Nanostructured porous silicon surfaces which possess an open pore morphology Neutral glycans tend not to produce ions from the common have been used to provide matrix-free laser desorption and used matrices such as DHB and THAP in negative-ion mode but will mainly for the analysis of small molecules (Tsao & DeVoe, do so from specific matrices such as nor-harmane or when 2011). adducted with anions such as chloride. Because fragmentation

Mass Spectrometry Reviews DOI 10.1002/mas 7 & HARVEY of negative ions from carbohydrates such as N-glycans is much V. IR MALDI more structurally informative than that of positive ions (Harvey et al., 2008), Domann et al. (2012) have compared several Water ice has been used successfully as a matrix for IR-MALDI- matrices mixed with the anions F ,Cl,Br,I,NO3 , MS but has not found general use because of the lack of the H2PO4 , and HSO4 . They found that THAP containing 1 M necessary cooled target. Pirkl et al. (2012) have addressed ammonium nitrate gave the strongest negative-ion spectra from the problem by developing a temperature-controlled sample N-linked glycans and produced profiles relatively free from stage for use with an orthogonal TOF mass spectrometer. The fragments. The [MþNO3] ions were subsequently fragmented stage utilized a combination of liquid nitrogen cooling and in a TOF/TOF instrument and gave comparable spectra to those counter-heating with a Peltier element, which allowed adjust- acquired by collision-induced dissociation (CID) following ment of the sample temperature between approximately electrospray ionization. 1208C and room temperature. The IR wavelength was Nishikaze et al. (2012c) have investigated the use of five optimized and the best performance was obtained at a wave- liquid matrices and nine anions (Cl ,Br ,I ,NO3 , HSO4 , length corresponding to the absorption maximum of liquid water H2PO4 ,BF4 ,PF6 , and SCN ) for production of negative of about 2.94 mm. The ionization was particularly soft as ions from neutral N-glycans and for their effect on fragmenta- exemplified by the analysis of non-covalently bound holomyo- tion. The most useful matrix in their hands was a mixture of globin, of ribonuclease B and of an IgG monoclonal antibody p-coumaric acid (18) and 1,1,3,3-tetramethylguanidine (7/14) (MW 150 kDa). Untypical for MALDI-MS, multiply proton- doped with ammonium nitrate. Glycans adducted with the larger ated species were observed for some of the investigated peptides 7/52 anions (e.g., I ,SO3 ) did not yield useful fragmentation and for lacto-N-fucopentaose II ( ) oligosaccharides. spectra. VI. MALDI IMAGING O MALDI imaging is one of the growing areas of the application of MALDI analysis, as illustrated by the reviews and related OH articles listed in Table 2. It is particularly useful for analysis of lipids, including glycolipids, particularly when these contain HO charged sugars or sulfate groups. A number of different matrices and application methods have been used. For example, Marsch- 18, Coumaric acid ing et al. (2011) have shown that 9-aminoacridine (9-AA, 6/18) (4-hydroxucinnamic acid) is a useful matrix for MALDI imaging of acidic compounds in

TABLE 2. Reviews and general articles on MALDI imaging

Subject Contents Citations Reference MALDI imaging mass spectrometry for General review, sample preparation, (Balluff et al., direct tissue analysis: technological 132 choice of matrix, spatial resolution, etc. 2011) advancements and recent applications MALDI tissue imaging: from biomarker Sample preparation, targeting specific (Cazares et al., 69 discovery to clinical applications compounds for biomarker discovery 2011) Matrix-assisted laser desorption Sample preparation for different lipid ionization imaging mass spectrometry in 162 types. Table of published applications 2011) lipidomics Sample preparation for mass Sample preparation, choice of matrix, 142 (Goodwin, 2012) spectrometry imaging problems that can occur Imaging mass spectrometry for Sample preparation. Application to (Goto-Inoue et 98 lipidomics different lipid types al., 2011) Instrumentation, sample preparation, MALDI-imaging mass spectrometry (Kaspar et al., table of applications to different plant 68 An emerging technique in plant biology 2011) material Use of mass spectrometry for imaging General review, instrumentation and (Lee et al., 125 metabolites in plants methodology 2012g) (Oppenheimer & Tissue analysis by imaging MS General review 123 Drexler, 2012) Development of imaging mass (Saito et al., Short review with a few applications 69 spectrometry 2012c) (Touboul et al., Mass spectrometry imaging General review, mainly applications 55 2011) Molecular imaging and depth profiling Comparison of SIMS, MALDI and (Vickerman, 102 by mass spectrometry. DESI 2011) Emphasis on CID, applications to MALDI imaging of lipid biochemistry in (Zemski Berry et different lipid types. Tables of 165 tissues al., 2011) applications, +ve and -ve ion CID.

8 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & negative mode. It displays high selectivity for low complexity Angel et al. (2012) have reported enhanced sensitivity sulfatides such as galactosylceramid-I3-sulfate (6/16)andis for lipids (including sulfatides and gangliosides) by use of suitable for quantitative analysis. With acidic fractions of lipid negative-ion MALDI. The tissue sections were washed with extracts and cryosections from kidneys obtained from both wild- volatile buffers at different pHs prior to deposition of the type and arylsulfatase A-deficient (ASA /) mice, the authors DHB matrix and MS. Washing with ammonium formate, pH showed that 9-AA also enables sensitive conventional on-target 6.4, or ammonium acetate, pH 6.7, significantly increased analysis as well as imaging of complex lactosylceramide-II3- the signal intensity by up to fivefold and the number of sulfate and gangliotetraosylceramide-II3,IV3 bis-sulfate. analytes recorded from adult mouse brain sections. Cerruti One potential problem with imaging of lipids is the et al. (2012) report that the use of 9-aminoacridine as a formation of both sodium and potassium cationized species. matrix in negative-ion mode gives superior results for lipid Cerruti et al. (2011) have proposed a new method, involving the imaging than the classical, DHB, THAP, or CHCA. In their use of lithium salts in the matrix solution to produce only work, 28 lipid species, including sulfatides, were imaged in lithium-cationized molecules. Of the five lithium salts that were rat brain. tested, lithium trifluoroacetate and lithium iodide emerged as Delvolve and Woods (2011) have optimized automated the best with the latter salt giving slightly increased desorption matrix deposition for detection of phosphatidylcholines and of phosphatidylcholines (19). A mixture of CHCA and the sulfatides in rat brain tissue slices using an inkjet spotter. lithium salt was used as the matrix, and this was sprayed onto Both DHB and 2,6-dihydroxyacetophenone (2,6-DHAP, the tissue section in one application. Images were acquired from 1/49) were suitable matrices but optimization was only rat brain tissue sections and it was found that more structurally performed with DHB (30 mg/mL solution in 50% EtOH). relevant fragments were generated by tandem mass spectrome- The optimum dwell voltage, dwell time, and air flow were try when analyzing lithium-cationized species than were found to be 29 V, 34 msec and 0.25 kPa, respectively. obtained with the other common adducts. Glycolipids were not Optimum matrix volume/spot was determined as 15 nL with examined in this work but there is no reason to suppose that a spot distance of 200 mm. these compounds would not also show improved behavior if Because current matrix deposition methods often result analyzed as lithium adducts. in non-homogenous surfaces, Mounfield and Garrett (2012)

O CH O O 3 P N OO CH3 O H3C

19, Phosphatidylcholine

Another problem with MALDI imaging is spatial resolu- have developed a fully automated method using an enclosed tion, which is dependent both on the size of the organic matrix spray chamber and a modiﬁed commercial atomizing spray crystal and of analyte migration during the matrix application nozzle combined with solenoid controlled valves and a process. To overcome these problems, Sugiura and Setou (2010) programmable logic controller to control and deliver the have developed nanoparticle-assisted laser desorption/ioniza- DHB matrix solution. Optical microscopic examination tion imaging in which the matrix crystallization process is showed a uniform coating of matrix crystals across the rat eliminated. Nanoparticles were prepared from FeCl2 4H2O and brain tissue sample. The resulting images were of better g-aminopropyltriethoxysilane (20), suspended in methanol with quality and more reproducible than from tissue specimens 10 mM sodium acetate, and sprayed onto the tissue samples with prepared by the inkjet deposition method. an airbrush. The method was applied to gangliosides and other Rather than using a spraying technique for matrix lipids in mouse brain sections and excellent resolution was deposition, Thomas et al. (2012) have investigated sublima- obtained. tion as a method for achieving a very even deposition of the matrix over the sample surface. Twelve, mostly common, CH3 matrices were investigated and 1,5-dihydroxynaphthalene O CH 3 (21) was found to be highly effective for lipid and O Si O glycolipids (glucosylceramide and gangliosides) analysis in NH2 both positive and negative-ion modes. Ion images were H C O 3 obtained from adult mouse brain and whole-body ﬁsh tissue sections in both modes from the same tissue section at 20, -Aminopropyltriethoxysilane 100 mm spatial resolution.

Mass Spectrometry Reviews DOI 10.1002/mas 9 & HARVEY

of a laser wavelength or voltage. DHB and 2,5-DHAP (1/43) OH gave the best results; THAP and 2,6-DHAP (1/49) were less useful. The method allowed gangliosides up to GQ1 (four sialic acid residues) to be analyzed with negligible sialic acid loss. The method was used to image GD1 ganglioside (22) in mouse brain in negative-ion mode. Methods have been designed to target speciﬁc compound OH types as illustrated by the work of Dai et al. (2011) who have developed a bis-boronic acid-containing compound that binds 21, 1,5-Dihydroxynaphthalene sialyl-LewisX antigens. This compound was linked to a trityl

OH OH OH HN O O OH O OH OH O O O O O NHAc HO HOOC OH HOOC O OH O OH OH HO O HO O HO HO HO AcHN HO HO AcHN HO

22, Ganglioside GD1a

A method combining enzyme digestion with MALDI has molecule with a photolabile linker (23) and used to profile the been developed by Yamada et al. (2012b) for the identification silyl-LewisX region of cancer tissue in kidney slices without the of oligosaccharides in paraffin-embedded histopathological use of a matrix. The positively charged trityl ion provided high sections. The samples of ileum in paraffin blocks were cut into sensitivity. 4-mm sections and mounted onto an indium tin oxide-coated Other examples of MALDI imaging are listed in Table 3. glass slide (Bruker Daltonics GmbH, Bremen, Germany). The samples were heated and washed with xylene to melt and VII. ION MOBILITY remove the paraffin. The sample was re-hydrated by graded washes with xylene and ethanol followed by washes of ethanol The incorporation of ion mobility into commercial instruments in water and finally with pure water. The sections were then has added another dimension to the analysis of biomolecules treated with 10 U/mL of a-amylase in 0.1 M phosphate buffer because of its potential to separate isobaric compounds accord- (pH 6.4) at 378C for 2 hr in a humidified chamber to reduce the ing to shape. Several applications to carbohydrate analysis have size of the polysaccharides and dried using a SpeedVac (Thermo appeared with some employing MALDI. Mobility cross- Scientific) at room temperature. The DHB matrix (50 mg/mL of sections of over 300 small carbohydrates have been determined DHB in 70% methanol and 0.1% TFA) was uniformly sprayed by Fenn and McLean (2011), and the technique has been shown over the samples using an airbrush. Spectra were recorded with to be capable of separating isomeric compounds in some cases. an Ultraflex II (Bruker Daltonics GmbH, Bremen, Germany) Collisional cross sections varied slightly with the different alkali instrument equipped with a 355-nm Nd:YAG laser using a 200- metals used to ionize the compounds but not in a linear manner Hz repetition rate. with increasing mass; rubidium showed a much lower cross A matrix-free method designed specifically for the detec- section than expected for the pentasaccharides LNFP1 (24) and tion of small molecules and termed platinum vapor deposition LNFP2 (7/52). Fragmentation was performed both before surface-assisted laser desorption/ionization imaging mass mobility separation (allowing cross section measurements on spectrometry (PVDSALDIIMS) has been performed using a fragment ions to be obtained) and afterwards. Ion mobility has commercially available magnetron sputtering device for Pt been shown to be advantageous for detection of low mass deposition. Vapor deposition of Pt produced a homogenous layer compounds ionized by MALDI as the result of matrix ion of nanoparticles over the surface of the target and was used for separation in the mobility space (Dwivedi et al., 2011). the direct detection of small analytes such as carbohydrates, As well as target compound separations, ion mobility has pigments and drugs separated by thin-layer chromatography proved to be an excellent technique for removing contaminating (TLC) without the need for extraction or concentration process- ions because many fall on different drift-time:m/z trend lines es (Kawasaki et al., 2012a). (Harvey et al., 2011b). Combined with negative-ion CID, this Gangliosides are difficult to analyze by MALDI because of technique provides a powerful method for structural determina- loss of sialic acid groups. Such loss has been reduced by tion of small amounts of N-glycans. Originally developed for Richards et al. (2012) who used a laserspray ion source. In this ESI, negative-ion CID of N-glycans has now been extended to inlet system, the matrix/analyte sample is ablated at atmospheric ionization by MALDI with a Synapt G2 (Waters Corp., Man- pressure, and ionization takes place in the ion transfer capillary chester, UK) instrument (Harvey et al., 2012). Negative-ion of the mass spectrometer inlet by a process that is independent spectra from neutral N-glycans were generated from THAP

10 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

H3CO

OCH3 O

NH S CH3 HO B N N O OH CH3 N N N

OCH3

O O

OH CH 3 O NH HO B N N CH3

doped with ammonium nitrate to yield nitrate adducts. Other determined. Isomers yielded mass-different rather than the ammonium salts such as ammonium chloride, bromide, iodide, abundance-different ions normally seen in positive-ion spectra, sulfate, and phosphate also gave good signals, but the adducts allowing isomers to be identiﬁed in mixed spectra. The method with the larger halogens or sulfate failed to fragment or gave was demonstrated with N-glycans released from the recombi- poor fragmentation spectra. The negative-ion CID spectra were nant human immunodeﬁciency virus glycoprotein, gp120. dominated by cross-ring cleavage ions and gave very informa- Among other compound types to have been examined by tive spectra from which the glycan structures were easily MALDI-IMS are gangliosides which have been studied in rat

TABLE 3. MALDI imaging Tissue Compounds Methods Notes Reference LTQ-Orbitrap Apples (Golden Flavonols, (CHCA), Bruker Use of intensity correlation (Franceschi et delicious) dihydrochalcones ImagePrep station to analysis to extract data al., 2012) spray matrix Arabidopsis -ve MALDI, Demonstrates accumulation of (Sarsby et al., thaliana flowers Glucosinolates TOF/TOF (9-AA), glucosinolates on outer 2012) and siliques TLC sprayer surfaces Black rice LTQ (DHB), Molecular species shown to (Yoshimura et Anthocyanins pericarp airbrush application distribute unevenly al., 2012a) Human Globotriaosyl- QIT-TOF (DHB), (Onoue et al., For diagnosis of Fabry disease endomyocardium ceramides spray 2011) L-TOF/TOF Following transient focal (CMBT), Airbrush (Whitehead et Mouse brain Gangliosides cerebral ischemia. Ganglioside for matrix al., 2011) expression may aid recovery application Lipids and Spiral-TOF/TOF (3- Use of the spiral-TOF for (Shimma, et Mouse brain glycolipids AQ/CHCA) imaging al., 2012) Laserspray (DHB, Laserspray to limit sialic acid (Richards, et Mouse brain Gangliosides 2,5-DHAP) loss al., 2012) R-TOF/TOF (9-AA), Sulfatides SM3 Development of 9-AA for (Marsching, et Mouse kidney ImagePrep and SB1a negative ion imaging al., 2011) matrix sprayer Toxic TOF/TOF (DHB), (Ha et al., Potato tuber DHB better than THAP glycoalkaloids picolitre sprayer 2012) Distribution of each Rabbiteye L-QIT (DHB), anthocyanin species were (Yoshimura et blueberry Anthocyanins Airbrush for matrix different in exo- and endo- al., 2012b) (Vaccinium ashei) application carp

Mass Spectrometry Reviews DOI 10.1002/mas 11 & HARVEY

OH OH OH O O O OH OH HO O OH O OH OH OH O HO O NHAc

HO O OH

24, LNFP1, (Fuc- -(1 2)-Gal- -(1 3)-GlcNAc- -(1 3)-Gal- -(1 4)-Glc)

brains (Jackson et al., 2011). The collision cross-sections of the 1. Reducing Terminal Derivatives Prepared by Reductive ions were a function of the number and position of sialic acids in Amination their oligosaccharide heads. MALDI-IMS analysis of a total 1/56 ganglioside extract from cerebrum detected all of the major brain The ﬂuorescent 2-aminobenzamide ( ) is frequently used to gangliosides. Additionally, comparison of a GD1a (21) standard label carbohydrates for HPLC separations. Its preparation with the isomeric GD1b (25) standard showed a clear shift to requires removal of excess labeling reagents before chromatography or mass spectrometry; a procedure that sometimes causes higher drift times for GD1a. Although GD1a and GD1b were not completely resolved by mobility, the change in drift time could problems. Benet and Austin (2011) have developed an on-line be used to give an indication of the ratio between GD1a and solid-phase extraction technique for reagent removal, whereby GD1b. The technique has also been used to show that ellagitan- labeled oligosaccharides were trapped on an amide stationary nins form aggregates in solution (Franceschi et al., 2011). phase in a small guard column and the excess reagents were washed away before the oligosaccharides were transferred to the VIII. DERIVATIVES analytical column for analysis. Although developed for HPLC analysis, the technique could be readily adapted for MALDI. 1/52 A. Reducing Terminal Derivatives 2-Aminopyridine ( ) derivatization also requires removal of unreacted label. Removal has been achieved in a one-step Although usually associated with adding ﬂuorescent labels to method using a MonoSpin Amide spin column (GL Sciences, glycans for detection after high-performance liquid chromatog- Tokyo, Japan) (Natsuka, 2012). raphy (HPLC) separation, reducing terminal derivatives have Various peptides and amines have been attached to sugars also found uses in mass spectrometry, for example, improving by Chang et al. (2011b) to increase sensitivity of detection. detection sensitivity. A review on ionization enhancement by Using maltoheptaose (7/11) as an example, amines were derivatization has been published by Iwasaki et al. (2011) (87 attached by reductive amination and oxidative amidation or by references cited) and a comprehensive general review (340 oxidative condensation with phenylenediamine (7/38) deriva- references) on carbohydrate derivatization has been published tives. Bradykinin, a vasoactine nonapeptide (RPPGFSPFR), and by Harvey (2011b). the tetrapeptide derivative, GFGR-OMe, (26) were found to be

OH OH OH HN O O OH O OH OH O O O O O NHAc HO OH HOOC O OH HO OH OH HO HOOC O O HO HO O AcHN HO HO HO AcHN HO 25, Ganglioside GD1b

12 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & excellent and gave between 45- and 273-fold increased ion þ NH NH abundance by MALDI-TOF-MS. [MþH] Rather than the more O common [MþNa]þ ions were formed as a result of ionization of H2N NH2 the peptide. The high signal enhancement was attributed to the NH COOCH3 high proton afﬁnity of the basic guanidino group in arginine moieties along with the hydrophobic property of the aromatic H2N moiety. The derivative 27 was also prepared using the corre- 28, Substituted o-phenylenediamine tag sponding substituted o-phenylenediamine (NH2)2Ph-ROMe, (28), to react with the sugar. The authors also successfully In addition to investigating (NH2)2Ph-ROMe derivatives, modiﬁed tri-, tetra-, and penta-galacturonic acids by reductive Chang et al. (2011b) have tagged maltoheptaose with aromatic amination with bradykinin allowing them to be detected in the carboxylic and sulfonic acids, such as 2-aminobenzoic acid (2- 1/57 31 0.1 fmol region. Treatment of a2!8-linked tetra-sialic acid in AA, )) and 2-amino-1-naphthalenesulfonic acid (ANS, ) acetic acid solution with the o-phenylenediamine-arginine tag and also shown greatly improved sensitivity using deprotonated gave the quinoxalinone derivative 29 accompanied by concur- [M H] ions in the negative mode. By conjugation with rent lactonization, again giving high detection sensitivity. bradykinin via reductive amination, the N-acetylglucosamine Reaction of the carbohydrates with unsubstituted o-phenyl- tetra- and hexa-mers showed great signal enhancement (134- enediamine in acidic solution has been used by Hung et al. and 181-fold) in the negative mode, although with only slight (2012b) to synthesize benzimidazole-tagged derivatives (30, enhancement (three- to four-folds) in the positive mode. Scheme 1) of glycans such as glucomannans and to improve SO3H detection sensitivities over over those obtained from free sugars NH and to enable larger glycans to be seen. 2

NH NH 31 O , 2-Amino-1-naphthylsulfonic acid

NH NH2 Kaneshiro et al. (2011) have used the liquid matrix 3-AQ/ Sugar Phe Gly NH COOCH3 CHCA to simultaneously derivatize and ionize N-glycans. Heating a mixture of the glycans in the matrix on the MALDI 26 , Peptide tag GFGR-OMe target produced a quantitative addition of 3-AQ to the reducing terminus enabling the compounds to be detected with higher NH NH sensitivity than by traditional methods. Ten attomole of a O monosialylated glycan was detected in negative-ion mode and NH NH2 an MS/MS spectrum was obtained. In an application of the NH COOCH3 Sugar method, Kaneshiro et al. (2012) have examined N-glycans from N human epidermal growth factor receptor type 2 in negative-ion 27, Derivative using substituted o-phenylenediamine mode. Neutral glycans were detected as [MþH PO ] ions and to react with the sugar 2 4 sialylated glycans as [MH], and quantitation was possible

OH O O

O O NH NH HO O HO O O O NH NH2 AcNH HO HO O O NH COOCH3 OH AcNH HO HO N AcNH HO 2

29, Derivative with tetra 2 8-linked tetrasialic acid

OH H2N OH OH OH N + HO O HO OH HO H2N HO OH NH 30

SCHEME 1.

Mass Spectrometry Reviews DOI 10.1002/mas 13 & HARVEY over the range 0.5–5000 fmol using the 2-AP derivative of a dominated by Y-type cleavage ions as the result of the localized mono-sialylated biantennary glycan as the internal standard. It charge on the derivative. was shown that the glycosylation pattern was significantly different between the enzyme from breast cancer cells and 3. Reducing Terminal Derivatives Involving controls. It has also been shown by Nishikaze et al. (2012b) that Oximes and Hydrazides fragmentation of these derivatives in negative-ion mode was much more informative than that in positive mode. Derivatization with pyrene has recently been used to improve Sugars have also been labeled with fluorescein-5-thiosemi- signal intensity (Nakamura et al., 2011b). Glycans were heated carbazide (32) by reductive amination to give the fluorescent with pyrene butanoic acid hydrazide (34) in methanol at 808C adduct with lex ¼ 495 nm, lem ¼ 517 nm. Optimum reaction for 90 min, followed by reduction with sodium borohydride. conditions were heating at 758C for 1 hr and the derivatives were Analysis was by MALDI-QIT-TOF MS from CHCA. These used to image polysaccharides transported in living cells (Zhang derivatives showed higher signal intensity with less fragmenta- et al., 2011k). tion than the same glycans derivatized with 2-AP and gave spectra in both positive- and negative-ion modes. O NH H2N NH NH NH2 O

COOH

HO OO 34, Pyrene butanoic acid hydrazide 32, Fluorescein-5-thiosemicarbazide

The substituted alkoxylamine 5-(2-((aminooxyacetyl)ami- 2. Reducing Terminal Derivatives Prepared by Schiff no)ethylamino)naphthalene-1-sulfonic acid (EDANS-O-NH2, Base Formation 35) has been synthesized and used to form a fluorescent oxime derivative with fully N,N,N-trimethylated chitosan. The struc- The first step in the reductive amination reaction is Schiff base ture of the product was confirmed by 1H NMR, fluorescence formation. Some investigators have used this reaction without spectroscopy and MALDI-TOF MS (Benediktsdottir et al., subsequent reduction to label carbohydrates. Thus, Lavanant 2012). and Loutelier-Bourhis (2012) have added acidified procaine (33) or procainamide (7/28) to DHB directly on the MALDI target to form the Schiff base derivative with the production of [MþH]þ NH H N O NH rather than the more usual [MþNa]þ ions. Incomplete reaction 2 was observed with 10% acetic acid in the solution, but changing O this to 1% phosphoric acid produced a single ion from each SO3H carbohydrate. The ion yield from the derivatives was thought to be equivalent to that of the [MþNa]þ ions from DHB without 35 derivatization, but the noise level was lower and the sample spot , 5-(2-((Aminooxyacetyl)amino)ethylamino) more homogeneous. naphthalene-1-sulfonic acid, EDANS-O-NH2

CH3 O 4. Reducing Terminal Derivatives Prepared by NCH3 Other Methods O Small carbohydrates have been reacted with a mixture of d0/d5- pyridine to produce a quaternized and labeled derivative (36). H2N The d0/d5-pyridine mixture was used as both solvent and reactant. The mixture of carbohydrate and d -pyridine was 33, Procaine 0 mixed with 20% Tf2O in dichloromethane and vortexed for Schiff base formation with ethidium bromide has been used 10 min. Simultaneously, another aliquot of carbohydrate was to produce a very sensitive detection system, demonstrated with derivatized in d5-pyridine. Equivalent volumes of each derivat- maltoheptaose and N-linked glycans (Tong et al., 2012). The ized sample were combined and mixed with the MALDI matrix increase in sensitivity was about sixfold and threefold, respec- for subsequent analysis by Fourier transform-ion cyclotron tively, when compared with the signals from 2-AB- or perme- resonance (FT-ICR) MS. The derivatization method signiﬁcant- thylated-derivatized maltohexaose. The high sensitivity was ly improved the detection sensitivity which was higher than that attributed to the hydrophobic nature of the aromatic system and obtained with Girard-type reagents (1/55) that are naturally to the constitutive cationic charge. Fragmentation spectra were charged (Wang et al., 2011f).

14 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

The use of anion- and cation-containing derivatives for quantitation is discussed in Section XI. Carbohydrate N

B. Derivatives of Other Sites 36, Pyridine derivative 1. Permethylation A method for labeling oligosaccharide mixtures with a fluorogenic pyrylium dye, Py-1 (37, Scheme 2), to enable Permethylation appears to be becoming increasingly popular for analysis by capillary electrophoresis (CE) and MALDI-TOF has glycan analysis by both MALDI and ESI. For MALDI, in been reported by Johannesen et al. (2012). The unreacted dye is particular, significant increases in sensitivity are produced as effectively non-fluorescent but when conjugated to the analyte it the result of increased hydrophobicity, although these can be displays strong fluorescence at 600–640 nm. Thus, removal of negated with small samples because of excessive losses during excess dye following labeling is not required prior to analysis cleanup. Desantos-Garcia et al. (2011) have addressed this requiring fluorescent detection. The labeling reaction was problem by modification of their original solid-phase permethy- performed in two steps. First, the oligosaccharides were reacted lation technique with a threefold reduction in the quantity of with ethylenediamine by reductive amination, following which, NaOH beads used in the permethylation column and by use of the remaining free primary amine was reacted with the dye an on-line C18 trapping column attached to a liquid chromatog- under basic conditions to form a pyridinium ion (38, Scheme 2). raphy (LC)/MS instrument. A 75% increase in signal intensity The reaction was applied to a mixture of maltooligosaccharides was reported for N-glycans from reference glycoproteins (fetuin, and good CE peak separation was obtained. Sensitivity by ribonuclease B, and a1-acid glycoprotein) and 73 N-glycans MALDI-TOF-MS analysis was good and enabled detection of were found in human serum compared with 63 following liquid– oligosaccharides with up to 58 glucose units. liquid extraction. The reduction in scale of the permethylation D- And L-monosaccharides have been derivatized as bis- reaction should be advantageous for MALDI analysis. indole derivatives (39) using aromatic C-alkylation reactions Hung et al. (2012b) have demonstrated increases with indole in acetic acid for compositional analysis and chiral in sensitivity and extension of the mass range over which resolution by ligand exchange capillary electrophoresis using several polysaccharides could be observed with DHB as the borate–cyclodextrin as a chiral selector. MALDI-TOF MS was matrix following permethylation. Compounds examined includ- used to characterize the products of reaction (Kuo et al., 2011). ed dextran, glucomannan, arabinoxylan, arabinogalactan, and b-1,3-glucan, isolated from nutritional supplements of Ganoderma lucidum and Saccharomyces pastorianus. NH Jeong et al. (2012b) have developed a method whereby OH solid-phase permethylation of protein-N-glycosidase F (PNGase OH F)-released glycans from standard glycoproteins or human HO serum was performed in a 96-well plate format. Analysis was by HO OH MALDI-TOF from DHB and the entire procedure could be carried out in less than 2 days. The method was validated with NH the glycoproteins chicken ovalbumin and porcine thyroglobulin and used to study sialylated glycans from the human prostate 39, Glucose-bis-indole derivative specific antigen (PSA).

CH3 BF4 O

Carbohydrate + H2N Carbohydrate NH + NH2 NH2 H3C

CH3 37 Carbohydrate NH N

H3C

SCHEME 2.

Mass Spectrometry Reviews DOI 10.1002/mas 15 & HARVEY

A method for preparing permethylated heparin disaccharides peptide backbone were derivatized on the MALDI target plate has been reported by Heiss et al. (2011). The problem with these using 1-pyrenyldiazomethane (PDAM, 7/46), thereby avoiding compounds is their anionic character, which makes them relative- complicated and time-consuming purification steps. After the only insoluble in DMSO, the solvent that gives the best results in plate PDAM derivatization, samples were subjected to negative- permethylation reactions. To overcome this problem, the authors ion MALDI-MS using the liquid matrix, 3AQ/CHCA. [MH] converted the sulfates to their triethylammonium salts, which Ions were detected as the predominant species without loss of were less polar. Similarly, the solubility of glycosaminoglycans sialic acid. The CID of the derivatized sialylglycopeptides from (GAGs) was found to be improved dramatically if the sodium hen egg yolk enabled the a2!3- and a2!6-sialylated com- counter ions were first exchanged with triethylammonium by pounds to be differentiated: a2!6-sialylation gave an abundant passage through the triethylammonium form of a strong cation- 0,2A-type product ion from the reducing-terminal GlcNAc exchange resin. It was important that the salts were completely residue, whereas a2!3-sialylated glycans gave a series of 2,4A/ dissolved in the DMSO prior to addition of the sodium hydroxide Y-type product ions, again from the reducing terminal, with loss base because this reagent was found to convert the GAGs back of sialic acids. Related to this method, the linkage-specific methyl to the sodium salts, which would not dissolve. However, if esterifying technique involving methanol and 4-(4,6-dimethoxy- the triethylammonium salts were completely dissolved before 1,2,3-triazil-2-yl)-4-methylmorpholinium chloride (DMT-MM, addition of the base, a clear solution was obtained. Analysis was 5/12) (Wheeler, Domann, & Harvey, 2009) has been used to by LC/MS but should also be applicable to MALDI. determine the linkage of sialic acids in the monoclonal antibody Hu and Mechref (2012) have made a comparative study of Nimotuzumab (Montesino et al., 2012). permethylated N-glycans derived from the model glycoproteins A method involving combined methyl esterification and ribonuclease B and porcine thyroglobulin (PNGase F-released) reducing terminal derivatization has been reported by Hirose et and of glycans from human blood serum using MALDI-MS, RP- al. (2011). PNGase F-released glycans were bound to BlotGly- LC-MALDI-MS, and RP-LC-ESIMS. Whereas the glycomic coH (Sumitomo Bakelite, Co. Tokyo, Japan) hydrazide beads profiles acquired with the three methods were very comparable and methyl esterification of the carboxyl groups of the sialic for the model glycoproteins, differences were found for the acids was performed by incubation with 100 mM 3-methyl-1-p- glycans from serum. Seventy-three compounds were detected by tolyltriazene (MTT, 6/23) in dioxane. Finally, glycans were RP-LC-ESI-MS from 250 nL of serum but only 53 and 43 released from the beads as O-benzyloximes by a transiminiza- structures, respectively, were identified using RP-LC-MALDI- tion reaction with O-benzyloxyamine hydrochloride (40). The MS and MALDI-MS analyses of the same sample. The glycans method was used to study N-glycosylation in 88 birds resulting that were detected only in the RP-LC-ESI-MS analysis were in the identification of 61 N-glycans. mainly those present in low abundances. In addition, RP-LC- NH2 HCl ESI-MS allowed separation of several structural isomers. O Adeuya and Price (2012) have used aqueous-based acylation with vinyl acetate (CH255CH–CO–CH3) to form a mixture of fully and partially acylated products from small sugars. Analysis by MALDI-TOF MS gave a series of ions separated by 40. O-Benzyloxyamine hydrochloride 42 mass units allowing the number of hydroxyl groups to be enumerated. There does not yet appear to be a consensus as to which of the methods for sialic acid stabilization is the most useful. Although the most widely used method is permethylation, this 2. Derivative Formation from Sialic Acids technique prevents the formation of the diagnostic fragment ions Glycans containing sialic acids are generally unstable under that are so useful from underivatized glycans. Simple methyl MALDI conditions as the result of the labile proton of the ester formation overcomes this problem while stabilizing carboxy group. Stabilization can be achieved by derivatization the sialic acids. However, the resulting CID spectra contain such as methyl ester formation as emphasized with glycans from abundant ions resulting from losses of methanol which can human serum in a study of cancer-specific changes in glycosyla- confuse spectral interpretation. Amide formation yields a more 2 tion (An et al., 2011). The use of H3-methyl-esterification stable product but with only a one mass unit change in moleculat produced suitable internal standards for quantification. weight; a feature that can be overcome by preparation of Another problem with fragmentation of sialylated glycans methylamides. in negative-ion mode is that they do not produce many of the diagnostic fragments seen in the spectra of neutral sugars. IX. GLYCAN ARRAYS These relatively uninformative spectra are, again, the result of the labile acidic protons. Preferential losses of these protons The use of glycan arrays is another growing area involving suppress the abstraction of hydroxylic protons which is the MALDI analysis. Oligonucleotide microarrays have been pro- initiation mechanism for formation of the diagnostic ions. duced en masse through well-established and reproducible Methyl ester formation partly restores the formation of diagnos- technologies with array features ranging in size from 14 to tic fragments, but the spectra were found to contain many ions 300 mm. However, immobilization of other molecules can lead produced by the loss of methanol leading to rather complex to more heterogeneous results and is generally restricted to profiles (Harvey & Rudd, 2011). contact printing, affording feature sizes of 100–200 mm. Huang A method for differentiating a2!3- and a2!6-sialylation et al. (2011b) have adapted the oligonucleotide technology by on glycopeptide-attached glycans has been developed by Nishi- attaching carbohydrates to peptide nucleic acids (PNAs) and kaze et al. (2011). The carboxyl group on the sialic acid and have produced two libraries containing 25 carbohydrate

16 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & fragments in 625 discrete combinations. The advantage of this A general strategy termed shotgun glycomics has been combinatorial assembly is that a broad diversity of carbohy- developed for the study of carbohydrate binding to proteins with drates can be readily explored from relatively small libraries. emphasis on glycosphingolipids (GSLs) (Song et al., 2011d). Furthermore, the commercial availability of custom microarrays GSLs (41, Scheme 3) were treated with ozone to generate free with up to one million unique oligonucleotide sequences avoids aldehydes (42) which were reacted with heterobifunctional the need for specialized equipment. This approach was said to p-nitrophenyl anthranilate (43) by reductive amination to form a lend itself to changing the distances between the ligands by derivative (44), bearing a p-nitrophenyl ester as an excellent varying the nucleic acid template. To construct the arrays, the leaving group. The derivative precipitated from the product investigators used carbohydrates bearing thiol groups at their mixture when treated with acetonitrile and, upon reaction with anomeric positions (glycosyl thiols) and coupled these, with the diamines (45), transformed to a ﬂuorescent GSL derivative (46), aid of mild bases, to PNAs derivatized with chloroacetamide which retained an alkyl amine that could be covalently coupled (Cl–CH2–CO–NH2). When synthesis was performed with 10 mg to appropriate surface such as glass slides. The microarrays of resin, 6 mmol of the glycan gave enough product for over one were interrogated with cholera toxin, antibodies, and sera from million microarray experiments. MALDI was used to analyze individuals with Lyme disease to identify biologically relevant the products of synthesis. O

Carbohydrate O 41 OH

O3 O

Carbohydrate O O 42 NO2 NH2 O OH O

43 O

Carbohydrate O NO2 NH O

OH O 44

H2N n NH2 45 O

Carbohydrate O NH O

OH NH n NH2

SCHEME 3.

Mass Spectrometry Reviews DOI 10.1002/mas 17 & HARVEY

GSLs that were subsequently characterized by MALDI-TOF NH2 HS mass spectrometry. Sanchez-Ruiz et al. (2011) have constructed glycan arrays 49, Mercaptoethylamine on commercially available gold-coated MALDI sample plates and used them to assay glycosyltransferase activity and lectin A method using a novel nanolayered substrate plate com- trapping. The plates were prepared by forming a self-assembling bined with a microarraying robot, custom software, and MALDI- monolayer of 1-undecanethiol, which then bound to hydro- TOF MS for high-throughput small molecule identification, phobically tagged N-glycans (47). The hydrophobic group was exemplified with, among other compounds, the carbohydrate stearic acid. THAP was found to be the best matrix with kanamycin (50), has been developed by Lee et al. (2011e). To detection limits in the order of 5 pmol. optimize system performance, five different compounds, spanning the m/z range of 195–1338, were spotted on 20,304 spots. The OH O initial spot identification rate was 99.85% (20,273 spots), and after O O a proofreading algorithm had been added, 100% of 20,304 spots NH and 101,520 molecules were identified. Using this optimized RO 4 15 HO OH system, 47 different compounds (m/z 138–1592) were spotted over 5076 spots and could be identified with 100% accuracy. 47, (R = remainder of carbohydrate) OH OH Immobilized boronic acids have frequently been used to HO OH O O capture carbohydrates. However, because boronic acids exist in NH2 the anionic form in alkaline media, electrostatic interactions can HO HO H2N OH O NH2 adversely affect binding of charged sugars. Liang and Liu O (2011) have developed what they refer to as a self-assembled H2N molecular team consisting of thiophene-3-boronic acid (48) and 49 mercaptoethylamine ( ) in which the nitrogen of the ethyl- 50, Kanimycin amine is positively charged while the boron is negatively charged at neutral pH. Thus, the net charge is 0 and electrostatic An assay addressing both neuraminidase activity and interactions are eliminated. The molecules were assembled on linkage (a2!3- versus a2!6-linked Neu5Ac) specificity by the gold surface of a MALDI target plate which was used for on- using whole influenza viruses (human A(H3N2) and avian plate purification of ribonuclease B (RNase B) from a mixture A(H5N2)) on a glycoarray is thought by the authors to be the containing RNase B and myoglobin. first of its type. The array was based on “DNA directed immobilization” (DDI) technology and was compared directly with a similar assay performed by MALDI-TOF. The results OH from both approaches were similar and showed that H3N2 B OH viruses presented a higher neuraminidase activity than H5N2 viruses and that the a2!3-sialyl lactose-DNA conjugate was a better substrate for both viruses (Pourceau et al., 2011). S Song et al. (2011c) have developed a method for fluorescently tagging glycans with 2-(N-aminoethyl)amino-benzamide 48, Thiophene-3-boronic acid (AEAB, 51, Scheme 4) with a procedure which maintains the

Cl OH OH O OH O O 54 O OH HO HO NH2 NH HO OH HO HO OH HO OH 52 53 55 O

NH2 O O3 OH O NH2 NH HO NH OH HO OH 51 O O NH O O HO NH HO OH NH 2 O NH 56

SCHEME 4.

18 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 4. Use of MALDI in arrays Carbohydrate Methods Notes Reference GalNAc 1 4(Fuc Glycan array used to identify glycan as potential (Aranzamendi TOF/TOF 1 3)GlcNAc-R antigen for serodiagnosis of trichinellosis et al., 2011) Glycans attached via 2-AA derivative (have open Glycans from Epoxy-silane (Lonardi et al., reducing-terminal ring). To study serum antibody glycoproteins slides, MALDI 2012) binding Underivatized or linker-derivatized lyso-GSL (Arigi et al., Glycosphingolipids TOF (DHB) immobilized on N-hydroxy-succinimide-or epoxide- 2012) activated glass slides GM1-related Functional interaction analysis of GM1-related (Kim et al., TOF (DHB) carbohydrates carbohydrates and Vibrio cholerae toxins 2012b) To study the donor specificity for the Neisseria Lactose on (Guan et al., SAMDI meningitidis 1,3-N-acetylglucosaminyl-transferase carbochips 2011) LgtA Neu5Ac-Gal- Comparison of MALDI-TOF and DDI array method (Pourceau, et TOF GlcNAc for influenza neuraminidase activity (see text) al., 2011) Phosphorylated TOF/TOF (Song et al., high-mannose For analysis of P-type lectins (DHB/TFA) 2012b) glycans Glycans immobilized via hydrophobic interactions on Plant cell wall an alkylthiol functionalised gold sample plate. Used to (Beloqui et al., TOF polysaccharides screen for glycosidase specificity in environmental 2012) samples Monolayer on (Laurent et al., Various For study of glycosyltransferase activity gold, TOF 2012)

closed-ring structure of the sugar. The sugars (52) were the liquid matrix, glycerol, to characterize the complex formed converted to glycosylamines (53) by reaction with ammonium between chito-oligosaccharide (CHOS) ligands with two var- bicarbonate and then treated with acryloyl chloride (54) to form iants of chitinase A (ChiA) from Serratia marcescens, the the glycosylamide 55. Reaction of this compound with ozone inactive E315Q mutant and the active W167A mutant, respec- yielded the keto-amide 56 which was then derivatized with tively. Results from IR-MALDI-o-TOF-MS were comparable AEAB by reductive amination to give 57. After purification of to those obtained using nano-ESI-quadrupole Q-TOF-MS, the labeled glycans, they were printed on a glass surface to but chitinase-CHOS complexes were not detected when UV- create a natural glycan microarray which could be used for MALDI was employed for desorption/ionization. The results studies on potential glycan-binding proteins. show that IR-MALDI-MS can be a valuable tool for fast and Further uses of carbohydrate arrays are listed in Table 4 and simple screening of non-covalent enzyme–ligand interactions. reviews of the topic are listed in Table 5. XI. QUANTIFICATION X. NON-COVALENT COMPLEXES A short review on quantitation of small molecules has been Transferring non-covalent complexes from the condensed phase published by Maki (2012). The ability of MALDI to produce into the gas phase is a challenging task because of the presence quantitative results is generally, but erroneously, regarded as of weak intermolecular bonds that have to be maintained during being poor because of factors such as target inhomogeniety and the phase transition. Currently, electrospray ionization is the different ionization efficiencies of the constituents in a mixture. preferred MS technique. IR-MALDI-MS also provides soft However, two papers, cited in the previous review, provided desorption/ionization conditions but is rarely used in this evidence that excellent quantitative results could be obtained context. Dybvik et al. (2011) have investigated IR-MALDI with using MALDI. Instrumental parameters also affect final ion

TABLE 5. Reviews on glycan arrays Subject Contents Citations Reference Construction and applications of (Campbell, Glycan and lectin microarrays 117 glycan and lectin arrays 2011) Carbohydrate microarrays, methods and Book, Methods in Molecular Biology - (Chevolot, 2012) protocols series Recent advances and future challenges in Short, introductory review to above (de Paz & 61 glycan microarray technology book Seeberger, 2012) Current advances in peptide and small Brief. Several compound types (Foong et al., 51 molecule microarray technologies including glycans and peptides 2012) Microarray-based technology for Construction, applications and (Gao et al., ? glycomics analysis problems 2012a)

Mass Spectrometry Reviews DOI 10.1002/mas 19 & HARVEY yields. To optimize the latter parameter, Unterieser et al. (2011) significant down-regulation of high-mannose glycans in the have studied various parameters relevant to quantitation by both metastatic cell line (Hahne et al., 2012). ESI and MALDI. For MALDI-TOF analysis, an equimolar mixture of malto-oligosaccharides (DP1-6), both native and derivatized with Girard’s T (GT, 1/55) reagent (positive ion) or 2-AA (negative ion), was analyzed using different matrices (2-(40-hydroxyphenyl)azobenzoic acid [HABA, 1/32], THAP, indoleacrylic acid [IAA, 3/5]) and super-DHB (sDHB), and laser power. Negatively charged 2-AA-labeled malto-oligosaccharides turned out to be unsuitable for quantification. Good results were achieved in positive-ion mode with the positively charged GT reagent with the best results bring obtained when OO the laser power was adjusted significantly over the desorption/ NH2 ionization threshold (1% deviation with GT label). In general, NH NH O HABA proved to be the best matrix. The useful dynamic range achieved by MALDI can be less than that from other ionization techniques. Dynamic range is set 59, Oxime tag mainly by instrumental parameters such as detector saturation and the range of the data system’s A-to-D converter. For A general method for the purification and quantitative ionization techniques producing steady beams of ions, signals glycomic analysis of human plasma has been developed by Tep can be accepted up to the limits of these parameters. With et al. (2012c). The 14 most abundant proteins (albumin, MALDI, on the other hand, each laser shot can produce very transferrin, haptoglobin, IgG, IgA, a1-antitrypsin, fibrinogen, different numbers of ions. If some of these shots produce a2-macroglobulin, a1-acid glycoprotein, complement C3, IgM, sufficient numbers of ions to saturate the detector, quantification apolipoproteins AI and AII, and transthyretin) were first will be compromised. Thus, the maximum signal strength that removed by multi-affinity chromatography (Agilent Technolo- can be tolerated, and hence the dynamic range, is reduced. For gies, Santa Clara, CA, MARS 14P column), and the lower quantification with an internal standard, probably about three abundant glycoproteins were enriched by multi-lectin affinity orders of magnitude is the useable range. chromatography (concanavalin A wheat germ agglutinin, and Zhang et al. (2011e) have performed relative quantitation jacalin. Glycans were released with PNGase F and derivatized 12 13 of linear and N-linked glycans with the use of (d0/d5)-phenyl-3- with [ C]- (normal plasma) or [ C]-2-AA (glycans from methyl-5-pyrazolone (PMP, 5/7) as derivatization reagents. The diseased states), giving a mass difference of 7 U, and monitored derivatization method was preferred to that involving reductive either by MALDI-TOF MS or HPLC with fluorescence detec- amination because of the instability of acid-labile groups such as tion. The method gave a 10-fold linear dynamic range for both sialic acid. It resulted in derivatives differing by 10 mass units. neutral and sialylated glycans with sub-picomolar sensitivity. Equimolar proportions of the various glycans yielded equivalent ion abundances and responses from derivatives mixed in XII. FRAGMENTATION different proportions gave a linear response over a 10-fold concentration range. Accuracy and precision values were A review on gas-phase dissociation of glycosylated peptide ions 5.1% and 8.34%, respectively. has been published by Dodds (2012). Stable isotope labeling has also been used to analyze the Rohmer et al. (2011) have prepared 3-AQ derivatives of N-glycans from human a-1-antitrypsin that had been recombi- several carbohydrates by a combined on-target derivatization nantly produced using various culture parameters. Per-13C- method (Rohmer et al., 2010) with harmine as the matrix and methylated glycans were used as internal standards whereas the have compared the different fragmentation techniques, CID, test glycans were permethylated with normal 12C-methyl iodide. pulsed-Q dissociation (PQD) and higher energy C-trap dissocia- This labeling method produced a mass difference of 29 U for the tion (HCD) with a MALDI LTQ Orbitrap (Thermo Fisher target biantennary glycan and avoided any isotopic overlap Scientific, Bremen, Germany) instrument in both positive þ þ þ (Blanchard et al., 2011a). ([M H] ions) and negative-ion ([M NO3] ions) modes. In Glycan quantification has also been achieved by labeling positive-ion mode, the spectra of underivatized linear carbohy- glycans at their reducing terminus with 13C and 15N-labeled drates were dominated by B/Z and C/Y ions whereas the spectra mass tags (5.0105 Da mass difference) bearing hydrazide- (58) of the derivatized compounds contained mainly Y-type ions as and aminooxy-functionalized groups (59, forming oximes). The the result of charge localization on the derivative. Abundant A- aminooxy tags outperformed the hydrazide reagents in terms type cross-ring fragments appeared in negative mode with all of labeling efficiency (>95% vs. 65% at 0.1 mM). Accurate three types of fragmentation. The spectra of branched com- quantification (CV < 15%) using MS1 but not MS2 spectra was pounds showed similar features. In all cases, the CID spectra achieved over a broad dynamic range (up to 1:40). Method contained the least abundant ions in the low-mass region of development was performed with glycans from ovalbumin and the spectra whereas spectra formed in the C-trap contained where needed, sialic acids were stabilized for MALDI analysis prominent oxonium ions. By combining the information by methyl ester formation (Powell & Harvey, 1996). The method from fragmentation of the derivatized glycans by all three was used to characterize N-linked glycosylation profiles of the fragmentation techniques, a complete structural characterization isogenic human colon carcinoma cell lines SW480 (primary in terms of linkage, branching, and anomericity could be tumor) and SW620 (metastatic tumor). The results showed achieved. The analysis of isomeric human milk oligosaccharides

20 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & derivatized with 3-AQ yielded comprehensive structural fragmentation was found to produce abundant fragments result- information. ing from the losses of the terminal galactose residues at the The oxonium ions observed with high mass accuracy in the reducing ends, showing that the galactosyl linkages are more C-trap spectra from the Orbitrap spectrum of glycopeptides labile than the other glucosyl linkages (Kwon, Lee, & Jung, have been combined with ions formed mainly by consecutive 2011). glycosidic bond cleavages in CID spectra to improve the The nature of the matrix can have a pronounced effect on detection and characterization of N-linked glycopeptides the type of ions produced by ISD. Thus, the oxidizing matrix, (Mayampurath et al., 2011). C-trap fragmentations overcome 2-hydroxy-5-nitro-benzoic acid (16), has been found to promote the low m/z cutoff inherent to quadrupole instruments, thereby fragmentation pathways from [MþNa]þ ions that involve revealing the presence of the glycan oxonium ions. Cross-ring mainly radical precursors. Both glycosidic and cross-ring cleavage information has not yet been detected in the C-trap. In cleavages were initiated by hydrogen abstraction from hydroxyl the report by Mayampurath et al. the software tool GlypID 2.0 groups on the carbohydrate to leave a radical site which then (Available at http://mendel.informatics.indiana.edu/chuyu/ initiated cleavage by radical-induced processes. These reactions glypID/software.html) that improves upon the original GlypID led to spectra containing many cross-ring cleavage products, tool by incorporating a novel scoring algorithm for C-trap similar to those seen in negative-ion spectra and which yield spectra is presented. This software combines three sources considerable structural information. The method was used to of information, the high accuracy MS precursor scan, the fragment milk sugars such as LNDFH-I (7/17) and LNDFH-II CID fragmentation scan and the C-trap fragmentation scan. (7/18) (Asakawa et al., 2012). The C-trap scoring algorithm could simultaneously identify the N-glycopeptide and predict the N-linked glycan structure B. CID type (high-mannose, complex, etc.). The peptide sequence and glycan composition could be determined through a mass-based 1. CID Fragmentation of Underivatized Carbohydrates searching of the peptide sequence in combination with a list of þ N-linked glycans based on biochemical rules. Low-energy CID of [MþNa] ions produces a wealth of mainly glycosidic fragments but usually only low abundance cross-ring cleavage products; the latter are most useful in defining linkage A. In-Source Decay (ISD) position. A comparative study of different tandem MS/MS A method, termed laser-enhanced ISD (LEISD) has been techniques for crocins and picrocrocin from the stigmas of reported to produce highly reliable and abundant fragmentation Crocus sativus L. has concluded that only high-energy collisions of neutral oligosaccharides on a MALDI-FT-ICR instrument (20 keV range) were capable of producing cross-ring cleavage using high (mJ level) laser power. The method was evaluated for products such as 0,4A and 3,5A ions (Koulakiotis et al., 2012). different laser powers with seven neutral oligosaccharides using Fragmentation of the aglycone (poly-unsaturated hydrocarbons) DHB as matrix. The higher laser powers produced the best ISD of these glycosides was not observed by any of the fragmenta- spectra and included fragment ions in the low-mass region. tion techniques that were investigated. Previous studies have Results from these experiments showed good signal-to-noise also emphasized the usefulness of high-energy processes for ratio and it was reported that more structural information could production of cross-ring cleavages in positive-ion spectra. In be obtained than by conventional CID. A-type cross-ring negative-ion CID, on the other hand, production of cross-ring cleavage fragments derived from the [MþNa]þ ions from fragments is a major process. linear oligosaccharides allowed distinction between a(1!4)-, ! ! ! a(1 6)-, b(1 4)-, and b(1 3)-linked isobaric structures. The 2. Photofragmentation method was applied to the analysis of two isomeric oligosaccharides from human milk (Yang et al., 2011c). In another study The fragmentation of deprotonated sialylated oligosaccharides on laser-enhanced ISD, glycosidic cleavages appeared to be and glycans from fetuin obtained by CID and 193 nm ultraviolet produced by thermal hydrogen radical transfer from the matrix, photodissociation (UVPD) in a linear ion trap have been as shown by deuterium labeling (Yang et al., 2012c). compared (Ko & Brodbelt, 2011). UVPD produced a more Metastable dissociation and prompt fragmentation of the extensive series of A- and X-type cross-ring cleavage ions and [MH] ion from D-fructose (1/16) have been studied by use of internal A/Y and X/B fragments than CID and, in addition, it 13 13 the isotope labeled molecules 1-[ C]-D-fructose, 2-[ C]-D- generated unique fragments by site-specific cleavage of the triol 13 fructose, and 6-[ C]-D-fructose. In prompt fragmentation substituent of the sialic acid residue. UVPD of doubly deproto- (<200 nsec), the negative charge was predominantly located at nated sialylated oligosaccharides produced mostly singly depro- the anomeric center (C2) with loss of C6-containing neutral tonated fragments, whereas doubly charged ions were the main particles. In metastable dissociation (8 msec), on the other products following CID. The larger array of product ions, hand, this type of fragmentation only applied to the production generated by UVPD relative to CID, was said to give greater of C4H4O3 (m/z 100). For the other metastable ions, most confidence for identification of glycans. fragments retained the charge at C6. Good correlation was found between predictions from classical dynamics simulations XIII. COMPUTER ANALYSIS OF SPECTRA and the experimental results (Flosadottir, Bald, & Ingolfsson, 2011). Much work has been devoted to the development of software Low molecular weight succinoglycan monomers, dimers, aimed at glycan identification, but the field still lags that for and trimers isolated from Sinorhizobium meliloti 1021 have other compounds, particularly proteins. Many laboratories been ionized in negative-ion mode from THAP. Prompt around the world are working on the problem and some of the

Mass Spectrometry Reviews DOI 10.1002/mas 21 & HARVEY developed tools are finding increasing application. However, envelope glycoprotein, CON-S gp140DCFI with very encourag- several of the tools attempt to identify glycans based on too little ing results. The software is freely available online at http:// evidence. Experimentally derived glycan masses are often glycopro.chem.ku.edu/GPGHome.php. matched to entries in databases and hits used as proof of glycan Bocker et al. (2011) have developed an algorithm for structure. Even with the use of biological species filters, this deriving the topology of a glycan solely from tandem MS data. method can lead to incorrect assignments and should not be used The program is based on fixed-parameter algorithms that can without additional structural information such as MS/MS, process a spectrum in a matter of seconds. It was used to exoglycosidase digestion, or, if sufficient material is available, determine the topologies of N-glycans from the serine protease by NMR. There are many examples in the literature of incorrect batroxobin from the venom of the viper Bothrops moojeni. structural assignments based solely on this approach (some Although the program produced 17 topologies for the 24 examples are listed in the tables). The measured mass only gives detected glycans, not all matched those determined experimen- the glycan composition in terms of isobaric monosaccharides tally. More data can be found at www.computer.org/publica- and if further information is not available, the results should be tions/dlib. left in this form. Nevertheless, such methods are still valuable in A tool, termed GlycoPP and available at http://www. that they highlight probable structures, but these structures must imtech.res.in/raghava/glycopp/, has been developed to predict be confirmed by orthogonal techniques. N- and O-glycosylation sites in prokaryotes. The program was Another ongoing problem, particularly in the area of N- developed from an extensive dataset of 107 N-linked and 116 glycans, arises from the depiction of structures. Many of these O-linked glycosites extracted from 59 experimentally character- reported structures are presented in symbolic form with the ized glycoproteins of prokaryotes. Using these datasets, majority of investigators choosing to adopt the recommenda- N-glycosites and O-glycosites could be predicted with an tions of the Consortium for Functional Glycomics. A major accuracy of 82.71% and 73.71%, respectively (Chauhan et al., deficiency with this system is that it fails to present the all- 2012). GlypID 2.0 is another software tool for characterization important property of linkage in a symbolic form. This failure of N-linked glycosylation sites of proteins. It uses several has led, for example, to some incorrect proposals for fragmenta- algorithmic approaches, such as accurate precursor mass and tion mechanisms when it is assumed that the angles linking the spectral data from both HCD and CID spectra, to identify symbols represent linkage positions. They do not in all cases. In peptides following tryptic digestion and to determine the this reviewer’s opinion, it is time for more precision in composition of the attached glycan. Further analysis results in a representing glycan structures, particularly for N-glycans. An predicted glycan structure. The installer and source code are alternative system that showed linkage was proposed in 2009 by available free at http://mendel.informatics.indiana.edu/~chuyu/ Harvey (2009) and was extended in 2011 (Harvey et al., 2011a) glypID/software.html (Mayampurath et al., 2011). to cover other glycan types with the added advantage that it The Glycolyzer is another glycan annotation package avoided the use of color allowing all symbols for the constituent designed mainly for biomarker discovery. The software consists monosaccharides to be readily used across various media of modules for data importing and exporting, FT-ICR signal including computer screens and paper. Basic monosaccharides preprocessing, internal calibration, noise threshold calculation, such as the various hexoses were shown with different shapes, peak picking, isotope grouping and filtering, glycan annotation, with modifications such as the addition of dots, crosses, or intensity normalization, missing value filling, multiple spectra fills used to indicate functional groups such as deoxy, acid, or averaging, hypothesis testing, and multiple testing corrections. N-acetylamino, respectively. Linkage was shown by the angle The glycans that pass the rigorous multiple tests are considered of the lines connecting the symbols with full lines indicating to be candidate biomarkers. The source code is available from b-anomericity and dashed lines used to show a-bonds. the authors’ web site at chemgroups.ucdavis.edu/lebrilla/ Examples of the use of this system are structures 66–80, 105, Glycolyzer.zip (Kronewitter et al., 2012). and 106. A novel algorithm for glycan structure prediction, particularly from compounds of low abundance, works by matching glycan isotope abundance. It takes isotope masses, A. Algorithms for Analyzing Spectra abundances, and spacing into account. A comprehensive data- Woodin et al. (2012) have developed a freely available software base containing 808 glycan compositions and their correspond- tool named GlycoPep grader (GPG) which is designed to ing isotope abundance was constructed and validated by accelerate the process of accurately determining glycopeptide analyzing the mouse kidney MS data from the Consortium for composition from tandem mass spectrometric data. The pro- Functional Glycomics. This analysis resulted in the identifica- gram identifies unique fragmentation patterns shown by glyco- tion of six more glycan compositions than the previous proteins carrying high-mannose, hybrid or complex N-linked annotation and significant improvement of detection of weaker glycans, and patterns specific to glycans carrying fucose or sialic peaks compared with the algorithm previously reported (Xu acid residues. The algorithm scores potential candidate compo- et al., 2012b). sitions of the same nominal mass against MS/MS data by GlycomeAtlas (Konishi & Aoki-Kinoshita, 2012) is a tool evaluation of the Y1 fragment ion and other peptide-containing for displaying structures of glycans that occur in various tissues product ions, across multiple charge states, when applicable. In of human and mouse. Data were acquired from the Consortium addition to analysis of the peptide portion of a given glycopep- of Functional Glycomics but can be augmented with users’ own tide, the algorithm predicts and scores product ions that result data. The user is presented with a diagram of human or mouse from unique neutral losses of terminal glycans. The program has and merely has to click on the target tissue for the glycan been tested with several well-characterized glycoproteins, structures (N-glycans are shown in the paper) to be displayed in including RNase B, asialofetuin, and transferrin, and the HIV symbolic form. Structures were obtained from ESI-MS/MS and

22 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

MALDI-TOF data; consequently, some linkage information is polysaccharide antigens and their antibodies is PolysacDB ambiguous. The software is available at http://www.rings.t.soka. (Aithal et al., 2012). At the time of publication, the database ac.jp/GlycomeAtlas/GUI.html. contained 1554 entries of 149 different antigenic polysacchar- The popular applications GlycanBuilder and GlycoWork- ides from 347 different microbes. It is freely available at http:// bench (Available at http://code.google.com/p/glycanbuilder) crdd.osdd.net/raghava/polysacdb/. A database for Drosophila that allow users to draw and investigate fragmentation of glycans N-linked glycopeptides (http://betenbaugh.jhu.edu/GlycoFly) have been updated (Damerell et al., 2012). named GlycoFly has been established as a resource for study of neurological disorders (Baycin-Hizal et al., 2011a). GlycoFish is a database of zebrafish N-linked glycoproteins (Baycin-Hizal B. Databases et al., 2011b) and can be found at (http://betenbaugh.jhu.edu/ A description of GlycomeDB, a database that integrates the GlycoFish). structural and taxonomic data of all major public carbohydrate A web-based data management system (GlycomicsDB) has databases, as well as carbohydrates contained in the Protein been developed that can incorporate large volumes of data from Data Bank has been published (Ranzinger et al., 2011). This several sources and organize them into a uniform format database is currently the most comprehensive and unified for users to store and access (Visvanathan et al., 2011). The resource for carbohydrate structures worldwide. It retains system enables participating laboratories to share raw MS data the links to the original databases and is updated at weekly and structural information of glycans, which members of intervals with the newest structures available from the source interdisciplinary teams can access. It is available at http://www. databases. The complete database can be downloaded freely or glycomics.bcf.ku.edu. accessed through a web interface (http://www.glycome-db.org). The Protein Data Bank (PDB) is currently the largest Four major structural query options are implemented namely database of biomolecular structures with about 71,000 entries of “exact structure search,” “substructure search,” “similarity which about 6% contain carbohydrates. Reading these files for search,” and “maximum common substructure search.” Struc- biomolecular simulation is often non-trivial because of the tural queries can be entered graphically, either using Glycan- inconsistency and complexity in the PDB file format for Builder (http://relax.organ.su.se:8123/eurocarb/gwb/builder. carbohydrate-containing structures. For example, the current action) as the default, or using DrawRINGS (http://rings.t. naming convention does not unambiguously identify anomeric soka.ac.jp). The query structure can also be specified using configurations and about 30% of carbohydrate structures contain different machine-readable encoding formats, among which at least one error regarding the carbohydrate-type assignment. are CarbBank, LINUCS, LinearCode, BCSDB encoding, and Furthermore, there are cases where the entire carbohydrate chain Glyde II (http://glycomics.ccrc.uga.edu/core4/informatics-glyde- is treated as a single residue. To address these issues, Jo et al. ii.html). (2011) have developed Glycan Reader and its web-based EUROCarbDB is a relational database containing glycan interface (http://www.charmm-gui.org/input/glycan) for reading structures, their biological context, and analytical data from PDB structure files with glycans by (i) detection of carbohy- HPLC, MS, and NMR. It is complemented by a suite of drates, (ii) automatic annotation of carbohydrates based on their glycoinformatics tools such as one for drawing glycan structures 3D structures, (iii) recognition of glycosidic linkages between in several symbolic formats. The test version of the web carbohydrates as well as N-/O-glycosidic linkages to proteins, interface to the EUROCarbDB can be found at http://www.ebi. and (iv) generation of inputs for the biomolecular simulation ac.uk/eurocarb (von der Lieth et al., 2011). program CHARMM with proper glycosidic linkage setup. In Another database based on human serum glycoproteins and addition, Glycan Reader is linked to other functional modules in containing over 300 structures has been constructed by the the CHARMM-GUI (http://www.charmm-gui.org), allowing Lebrilla group and used as a base for N-glycan analysis using users to easily generate protein/carbohydrate complexes or conventional exoglycosidase and mass spectral fragmentation glycoprotein molecular simulation systems in solution or data (Aldredge et al., 2012). As well as structure, the library membrane environments and to visualize the electrostatic contains accurate masses and HPLC retention times. Glyco- potential on glycoprotein surfaces. ProtDB is a database containing about 2500 glycoproteins from A critical analysis of data in the CarbBank database has mouse (Kaji et al., 2012). found that about 35% of the records contain errors and the The bacterial carbohydrate structure database (BCSDB) is authors conclude that data contained in the database cannot, another open-access project that collects primary publication therefore, be used and referenced without verification (Egorova data on carbohydrate structures originating from bacteria and & Toukach, 2012). Lists of databases and other tools for includes their biological properties, bibliographic, and taxonom- glycobiology have been published in several reviews (Lutteke,€ ic annotations, NMR spectra, etc. The project contains its own 2012; Mazola et al., 2011; Yamada & Kakehi, 2011; Artemenko glycan description language and the paper includes a full et al., 2012). description of the interface and problems that can occur from incomplete or erroneous glycan descriptions. It is available from XIV. STUDIES ON SPECIFIC CARBOHYDRATE http://www.glyco.ac.ru/bcsdb3/ (Toukach, 2011). ProGlycProt TYPES (http://www.proglycprot.org/) is an open access, manually curated, comprehensive repository of bacterial and archaeal A. Mono- and Oligo-saccharides glycoproteins with at least one experimentally validated glycosite (glycosylated residue) providing an extensive compilation Applications of MALDI to the analysis of oligo-and polysac- of 334 experimentally identified glycosites and glycoproteins of charides have been reviewed by several authors and are listed in prokaryotes (Bhat et al., 2012). Another database of microbial Table 6.

Mass Spectrometry Reviews DOI 10.1002/mas 23 & HARVEY

TABLE 6. Reviews on the use of MALDI for the analysis of polysaccharides Subject Comments Citations Reference Structural analysis only occupies a (Aachary & Xylooligosaccharides: Synthesis, structural small section of the review which 162 Prapulla, characterization and applications covers use of the sugars as a prebiotic 2011) Characterization of plant cell wall Mainly applications 61 (Bauer, 2012) polysaccharides by mass spectrometry Covers nomenclature, elemental (Daraghmeh et Chitin analysis, synthesis, physical 61 al., 2011) properties, analytical methods, uses. Mass spectrometric characterization of (Mischnick, General review 190 oligo- and polysaccharides 2012) Chitooligosaccharides: Synthesis, General review, small section on (Mourya et al., 307 characterization and applications MALDI analysis 2011) Sample preparation and current applications of liquid chromatography for (Raessler, MALDI in mass spectrometry section 60 the determination of non-structural 2011) carbohydrates in plants Fractional purification and bioconversion Several references to MALDI analysis (Peng et al., 323 of hemicelluloses of hemicelluloses 2012a) General review on occurrence and Polysaccharides of the red algae - (Usov, 2011) structural analysis

A comparison between TLC, GC/MS, and matrix-free material-enhanced laser desorption/ionization time-of-flight OH OH mass spectrometry (mf-MELDI-MS) for the determination of OH small carbohydrates in medicinal plants, as exemplified by HO compounds obtained by microwave-assisted water extraction of OH OH Quercus, has been presented by Qureshi et al. (2011). TLC analysis proved the presence of mono-, di-, and tri-saccharides 60, Mannitol and hinted at the existence of a larger carbohydrate. However, Two papers (Golon & Kuhnert, 2012a,b) have reported resolution was poor. After evaluation of different derivatization compositions of caramel, one of the best known dietary techniques, GC-MS of TMS-oximes confirmed the presence of materials obtained from carbohydrates by heating. In the first the mono- to tri-saccharides, but the carbohydrate of higher (Golon & Kuhnert, 2012b), the authors investigated caramel oligomerization degree could not be found. mf-MELDI-MS formed by heating glucose, fructose, and saccharose and found further confirmed the presence of the above carbohydrates up to that the caramel is composed from several thousand compounds trisaccharides and hinted at the presence of a trisaccharide formed by a small number of unselective and chemoselective together with additional information on the composition of reactions. Caramelization products were found to include the sample. Quantitative determination by GC/MS resulted oligomers with up to six carbohydrate units formed by reactions in 1.750, 1.736, and 0.336 mg/mL for glucose, sucrose, and such as unselective glycosidic bond formation, dehydration of raffinose, respectively. oligomers with loss of up to eight water molecules, hydration, Biological materials such as vaccines, probiotics, and disproportionation, and the formation of coloured aromatic biopesticides generally require stabilization to retain activity compounds. In the second paper (Golon & Kuhnert, 2012a), or viability in a dry form. Stabilizers for such microbial caramelization of sucrose, lactose, and maltose was studied with preparations generally include one or more small carbohy- similar results. drates such as the sugar alcohols (mannitol [60] and sorbitol [1/42]) and the disaccharides (lactose [7/67], sucrose [7/6], B. Polysaccharides and trehalose [3/39]). Wunschel et al. (2011) have developed a method for detection of these simple carbohydrates using Practical details for obtaining MALDI-TOF spectra of the MALDI-MS and GC/MS. The native carbohydrates and products of cellulose- and xyloglycan-hydrolyzing enzymes other constituents were detected by MALDI-MS as a have been published (Pena~ et al., 2012b). screening tool and analyzed in detail by derivatization and Several reports have determined optimal conditions for GC/MS detection. Both techniques were tested against 10 extracting various carbohydrates from different media. Thus, different types of stabilization recipes with Yersinia pestis microwave-assisted extraction has been used to recover sulfated cultured on different media as the biological component. polysaccharises (fucoidan) from the brown seaweed Fucus Several additional components including proteins and pep- vesiculosus (Rodriguez-Jasso et al., 2011). Extraction at 120 psi tides from serum or milk, polymers (e.g., poly-vinyl- for 1 min, using 1 g seaweed in 25 mL water, gave the best pyrrolidone), and detergents (e.g., Tween) (Available from recovery. Fucose (1/7) was found to be the main constituent of most scientific suppliers) were included in the formulations. this polysaccharide, with xylose (1/3) and galactose (1/6) The accuracy of the method was 98% for MALDI-MS and present in lower abundance. Statistical analysis (response 100% for GC/MS. The repeatability for detection of surface methodology) has assisted the optimization of condi- carbohydrates by MALDI-MS was determined to be 96%. tions for polysaccharide recovery from the roots of Isatis

24 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & tinctoria L. (woad, Brassicaceae) using hot deionized water. formation of the cell wall galactan, which is a linear polysaccha- The optimal conditions were an extraction temperature of ride consisting of 20–40 repeating D-Galf residues. The method 99.58C, an extraction time of 3.75 hr, and a ratio of water to consisted of reacting a disaccharide acceptor with a C12-carbon raw material of 11.84 (v/w). Under these conditions, the chain terminating in OPh (61) (the “light substrate”) with UDP- maximal observed extraction yield was 11.19 0.04%, which Galf in the presence of the enzyme for a time t1. A “heavy was in agreement with the predicted value of 11.17% (Han, substrate” in which the phenyl ring was labeled with deuterium Jiang, & Zhang, 2011). Extraction of polysaccharides from the was added and the reaction allowed to proceed for a longer time fruiting body of the fungus Tricholoma matsutake has been (t2). The products were analyzed by MALDI-TOF MS. The carried out using enzyme-assisted extraction methodology with deuterium-labeled product was found at a lower concentration the same statistical method. The optimum extraction conditions showing that it did not compete effectively for the enzyme were an extraction temperature of 61.88C, an extraction pH of indicating that the synthesized polymer maintained contact with 4.14, and an extraction time of 3.2 hr. Under these conditions, the enzyme and that the process was processive. Further studies the an experimental yield of polysaccharides was 7.53 0.26%, suggested that GlfT2 possesses subsites for Galf residue binding which was in close agreement with the value predicted by the and that substrates that can fill these subsites undergo efficient model. processive polymerization. The presence of these subsites and a The feasibility of using atmospheric pressure matrix- kinetic lag phase was proposed as common features of assisted laser desorption/ionization with ion trap mass processive enzymes and the authors anticipated that their spectrometry (AP-MALDI-ITMS) for analysis of plant-derived method could be applied to mechanistic studies of other oligosaccharides has been investigated by Chong et al. (2011). carbohydrate polymerization reactions. The method was able to detect xylooligosaccharides (XOS) with MALDI-TOF analysis of glycans produced from barley chain length of up to 10 xylopyranosyl residues. Although starch granules when treated with amylases has been used as a conventional MALDI-TOF MS showed better sensitivity at reference for showing that gravitational field flow fractionation higher mass range (m/z > 2000), AP-MALDI-ITMS appeared to can be used as a simple and cheap method for monitoring be more suitable for detection of acetylated xylooligosacchar- changes in the distribution of the starch granule size during ides. The structures of two isomeric aldotetrauronic acids and a amylolysis (Mazanec et al., 2011). mixture of acidic XOS were elucidated by AP-MALDI-ITMS The extraction efficiencies of physical extraction (room- using multi-stage mass fragmentation up to MS3. In addition, temperature centrifugation and high-speed centrifugation) and the method was combined with the direct endo-1,4-b-D-xylanase chemical extraction using EDTA and formaldehyde for exopoly- hydrolysis of plant material followed by AP-MALDI-ITMS saccharides from bacteria have been compared. Chemical detection. This method was shown to recognize the substitution extraction methods were found to be more efficient than the variations of glucuronoxylans in hardwood species and in physical extraction methods and of the chemical extractants, Arabidopsis thaliana which, to the authors’ knowledge, was the EDTA was found more effective than formaldehyde and gave first report to demonstrate the acetylation of glucuronoxylan more polysaccharide peaks using both ESI- and MALDI-TOF in A. thaliana. AP-MALDI-ITMS has also been used to show analysis (using CHCA as the matrix). Detection by ESI-MS was that acetyl xylan esterase enhances the solubilization of xylan very effective for compounds <300 Da whereas MALDI-TOF and enzymatic hydrolysis of wheat straw and giant reeds MS was found to be more suitable for rapid analysis of the (Arundo donax) (Zhang et al., 2011c). polysaccharides above 400 Da (Gedda et al., 2012). MALDI MS has provided evidence as to how polymerases Other applications of MALDI analysis to oligo- and poly- control the length of the polysaccharides that they synthesize. saccharide research are listed in Tables 7 (plants and animals) One fundamental issue is whether an enzyme is a processive and 8 (bacteria and other lower organisms). polymerase that maintains contact with the glycan substrate through successive monomer additions or distributive polymer- C. Glycoproteins ase. Experiments have been carried out by Levengood, Splain, and Kiessling (2011) on GlfT2, a glycosyltransferase essential Analysis of glycoproteins is one of the most important areas for cell wall biosynthesis in Mycobacterium tuberculosis,to to which MALDI MS has been applied as reflected by the obtain information on the mechanism. GlfT2 catalyzes the large number of reviews listed in Table 9. The field is complex

O O O

O OH O OH OH HO OH OH OH

Mass Spectrometry Reviews DOI 10.1002/mas 25 & HARVEY

TABLE 7. Use of MALDI MS for research on carbohydrate polymers from plants and animals (alphabetical by species) Species Carbohydrate Methodsa Notes Reference Adiantum Mannans, TOF, HPAEC- (Silva et al., Structural determination raddianum (Fern) xyloglucan PAD 2011) (Michel-Cuello Agave salmiana Fructans TOF (DHB) Study of enzymatic hydrolysis et al., 2012) Endo- -(1 4)-D- Structural determination. High mannanase, level of acetylation appears to Aloe vera Mannans TOF/TOF correlate with immuno- 2012) (DHB/CMBT) stimulatory activity Structural determination and Amorphophallus (Albrecht et al., Glucomannans TOF/TOF study of the action of enzymes konjac (Konjac) 2011) from fecal bacteria Arabidopsis O-Acetylated Endoglucanase, R- Increase in OAc during dry fruit (Louvet et al., thaliana xyloglucans TOF (DHB) development 2011) Ident. of enzyme producing XG Arabidopsis Xyloglucans TOF (DHB) with higher proportion of non- thaliana fucosylated subunits. 2011) IRREGULAR XYLEM (IRX15) and IRX15L encode DUF579- Arabidopsis CjXyl10B (Brown et al., Xyloglucans containing proteins - essential thaliana Xylanase, TOF 2011a) for normal xylan deposition in the secondary cell wall Trichoderma viride 4-O-Methylation of GlcA Arabidopsis (Urbanowicz et Glucuronoxylan endoxylanase, TOF catalyzed by unknown thaliana al., 2012) (DHB) function family 579 protein Arabidopsis Several enzymes, Structural determination of (Tryfona et al., Arabinogalactans thaliana TOF (DHB) arabinogalactans in leaf 2012) Xyloglucan axy8 mutant encodes an - Arabidopsis Xyloglucans hydrolyase, TOF fucosidase active on thaliana 2011b) (DHB) xyloglucans XTH31, encoding an in vitro Arabidopsis Xyloglucanase, XEH/XET-active enzyme, (Zhu et al., Xyloglucans thaliana TOF (DHB) shown to regulate aluminium 2012c) sensitivity Investigation of changes in Arabidopsis Xyloglucan specific cell wall biomechanical (Park & Xyloglucans thaliana endoglucanase, TOF properties in xyloglucan- Cosgrove, 2012) deficient xxt1/xxt2 mutant New GalA-containing Arabidopsis Cellobiohydrolase, Xyloglucans xyloglucan involved in root thaliana TOF (DHB) 2012a) hair tip growth Mutations in multiple XXT Arabidopsis genes of Arabidopsis reveal (Zabotina et al., Xyloglucans TOF (DHB) thaliana the complexity of xyloglucan 2012) biosynthesis Xyloglucan- Arabidopsis specific Description of experimental thaliana Xyloglucans details for mass profiling of cell endoglucanase and 2011a) (Hypocotyl) wall polysaccharides others, TOF

Artemisia (Guo et al., Glucomannan R-, L-TOF (DHB) Structural determination sphaerocephala 2012b) Krasch Asparagus Comparison of profiles in (Suzuki et al., Fructans TOF (DHB) officinalis different types of root 2011c) Pectin lyase and Method for enzymatic Homo- rhamno- production and effects on Beta vulgaris galacturonides (Holck et al., galacturonan I human faecal microbiota (sugar beet) and rhamno- 2011b) lyase, R-TOF/TOF composition after in vitro galacturonides (CHCA) fermentation Feruloylated and Shown to selectively stimulate Beta vulgaris nonferuloylated the growth of Bifidobacterium (Holck et al., TOF/TOF (DHB) (sugar beet) arabino- spp. in human fecal in vitro 2011a) oligosaccharides fermentations Beta vulgaris Oligosaccharides (Abe et al., TOF (DHB), NMR Structural determination (sugar beet) from molasses 2012b) Autohydrolysis, Characterization of (Testova et al., Betula ssp. (Birch) Hemicelluloses TOF autohydrolysis products 2011)

26 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 7. (Continued) -D-Frup- [(2 1)- -D- Isolation and structural (Xu et al., Blume riparia TOF Fruf-1-]7- -D- determination 2011c) Glcp ( -D-Frup) - -D- Isolation and structural (Xu et al., Blume riparia 7 TOF, GC/MS Glcp determination 2011b) Investigation of mechanism of Oligo- R-TOF/TOF Capsicum annuum infection by Xanthomonas galacturonides (DHB) -ve 2012) campestris Endopoly- Method to resolve Homo- galacturonase II, homogalacturonans based on (Ralet et al., Citrus galacturonans R-TOF/TOF their methyl esterification 2012) from pectin (DHB) pattern -1,4- Absorbed intact through by the (Kanatani et al., Coconut flour TOF/TOF (CHCA) Mannobiose rat portal vein 2012) Hydrothermal Structural determination. Eucalyptus Xylo- processing, R-TOF Neutral and acidic. Degree of globulus oligosaccharides 2011) (DHB), IR, NMR OAc about 0.6 Fagus crenata Oligosaccharides Investigation of action of hot (Yamauchi & Hot water, TOF (Japanese beech) from cellulose compressed water Saka, 2011) Study of hydrothermal (Asaoka & Gossypium Hydrothermal Cellulose saccharification in dilute Funazukuri, species (cotton) (HCOOH) TOF aqueous formic acid 2011) Comparison of arabinoxylan Endoxylanase, (Kulkarni et al., Grasses, various Arabinoxylan structure in bioenergy and TOF (DHB) 2012a) model grasses Gymnosperms, Xyloglucans Endo-(1 4)- - Structural determination from (Hsieh & Harris, monilophytes and from primary glucanase, TOF 28 species 2012) lycophytes cell walls (DHB) Harvest year shown to have a Malus domestica major impact on cell wall (Galvez-Lopez et Hemicelluloses TOF/TOF (s-DHB) (apple) polysaccharide composition al., 2011) and structure. Characterization of Ophiopogonis Oligosaccharides TOF oligosaccharides for (Li et al., 2012d) japonicus antidiabetic studies in rats Panax ginseng Water-extracted Characterization and TOF (DHB) (Jiao et al., 2012) C.A.Meyer oligosaccharides immunostimulating effects Panicum virgatum Experimental details for (Mazumder et Heteroxylans TOF (DHB), ESI (Switchgrass) structural characterization al., 2012) Manufacture and properties of Pinus pinaster Hydrolysis, (Rivas et al., Hemicelluloses bifidogenic sugars. Potential (Spanish conifer) TOF/TOF (DHB) 2012) food products Identification from molasses Galactogluco- R-TOF (DHB), (Price et al., Pinus taeda by-product of pine fiberboard mannans NMR 2011) production Populus Xylo- -Endoxylanase, Investigation of genes (Lee et al., trichocarpa oligosaccharides TOF (DHB/HIQ) involved in biosynthesis 2011c) (Poplar) Populus sp. Experimental details for (Mazumder, et Heteroxylans TOF (DHB), ESI (Poplar) structural characterization al., 2012) Compositional and structural Cell wall Endo-1,4- - differences found between Prunus persica polysaccharides glucanase, TOF parents and their related (Lahaye et al., (peach, 4 (hemicelluloses (DMA/DHB, s- genotypes. Also structure of 2012b) varieties) etc.) DHB) homogalacturonan and xyloglucan Glucose, sucrose TOF/TOF (matrix (Qureshi, et al., Quercus Comparison of methods and raffinose free), GC/MS, TLC 2011) Study of fermentation on Radix (Lin et al., Oligosaccharides TOF glycan content and Ophiopogonis 2011b) hypoglycaemic activity

Mass Spectrometry Reviews DOI 10.1002/mas 27 & HARVEY

TABLE 7. (Continued) Radix Polysaccharid- Studies on the antidiabetic (Linwei et al., TOF/TOF (DHB) Ophiopogonis rich extract activity 2012) Comparison of cell wall Xyloglucanase, (Zhang et al., Rice spp. Hemicellulose monosaccharides in wild and TOF (DHB) 2012f) cultivated rice Acid hydrolysis, To prepare oligomers for Shrimp (shell) Chito-oligomers (Li et al., 2012b) TOF (DHB) antioxidant study Hemicelluloses, Hemicellulose fine structure Solanum xyloglucan and Endo- -1,4-D- shown to be affected (Lahaye et al., lycopersicum glucomannan, glucanase, TOF, differently during ripening of 2012a) (tomato) galacto- PSD tomato lines with contrasted oligomers. texture Starch (cross- Solanum Pullulanase, - and linked and Study of substituent (Zhao et al., tuberosum hydroxy- -amylase, TOF distribution 2012a) (potato) (DHB) propylated) Prehydrolysis in softwood Galacto- pulping shown to produce a (Saadatmand et Spruce TOF (DHB) glucomannans valuable biorefinery fraction al., 2012) for material utilization Structural determination. Stevia rebaudiana Fructo- TOF/TOF (DHB), Mainly (2 1)-linked -Fruf, (de Oliveira et (Bert.) Bertoni oligosaccharides ESI, GC/MS with terminal -Glcp and - al., 2011) Fruf units Tamarindus Glycans shown to stimulate - indica L. Xyloglucans MALDI root elongation and shorten et al., 2012) (tamarind) seeds cell cycle in higher plants -1,3-glucan with low degree of polymerization involved in L-TOF (DHB), Tobacco -1 3-Glucans rapid defence responses, high (Fu et al., 2011b) FAB DP -1,3-glucan caused longer term effects. Analysis of A- and B-type Triticum spp. Amylose and (Yin et al., TOF starch granules in wheat (wheat) amylopectin 2012a) endosperm Triticum spp. Supplementation of xylanase (wheat) and giant AP-MALDI-Ion with xylan esterase shown to (Zhang, et al., Xylan reed (Arundo trap (DHB) enhance the solubilization of 2011c) donax) xylan Triticum spp. Debranched Characterization of A- and B- (Yin, et al., TOF (wheat) cultivars amylopectins type starch granules 2012a) Triticum spp. (wheat) and R-TOF (DHB), Use of commercial enzymes to (Makaravicius et Arabinoxylans Secale HPLC produce oligosaccharides al., 2012) cereal (Rye) Tulipa gesneriana Soluble sugars (Nonami et al., MALDI Structural determination (Tulip) from bulbs 2011) Hexose oligosaccharides, FT-ICR (DHB), Structural determination in red (Bordiga et al., Wine xyloglucans, GLC and white wines 2012) arabinogalactans KOH hydrol. Characterization of Xylans from (Van Dongen et Zea mays TOF/TOF, (DHB), substituents (Ara, GlcA, cobs and stover al., 2011) HPAEC, HPSEC, ferulic and coumaric acids) Depolymerized Commercial chitosans with Antibacterial activity against TOF (DHB) sample lysozyme and Campylobacter jejuni 2011) chitosanase Study of mechanochemical Commercial (Kireeva et al., Amylose L-TOF degradation. Cleavage at sample 2011) crystal boundary zone Commercial Acid hydrolysis, Study of acid hydrolysis in (Dee & Bell, Cellulose sample TOF (DHB) ionic liquids 2011)

28 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 7. (Continued) Fructo- TOF (DHB for Commercial Characterization as food (Borromei et al., oligosaccharides fructans, 3-AQ for sample ingredients 2011) and inulins inulins) Investigation of immune- Cellulase, Commercial -Glucans from stimulation caused by (Rieder et al., lichenase, sample cereals contaminants in carbohydrate 2012) TOF/TOF (DHB) preparations Commercial (Stovbun et al., Hexasaccharide TOF Physicochemical properties sample (Panavir) 2012) Product of sucrose and cellobiose, To study the effects on the (Ruiz-Matute et Synthetic catalyzed by R-TOF (DHB) growth of human gut bacteria al., 2011) Leuconostoc mesenteroides dextransucrases R-TOF/TOF To study the effect of roasting (Moreira et al., Synthetic Galactomannans (DHB) on coffee galactomannans 2011) Use of MALDI for investigating mechanism of (Ciric et al., Synthetic Amylopectin TOF (DHB) the enzymatic polymerization 2012) of polysaccharides Depolymerization of cellulose shown to be assisted by a (Benoit et al., Unspecified Cellulose TOF nonthermal atmospheric 2011) plasma Colloid-based multiplexed Cellobiose, screening for plant biomass- (Reindl et al., Unspecified cellotetraose, and TOF/TOF degrading glycoside hydrolase 2011) xylobiose activities in microbial communities Various, Oligosaccharides Structural derermination. -D- fermented with -D- TOF (DHB), GLC, (Okada et al., Fruf-(2 6)-D-Glcp identified beverage from fructofuranoside NMR 2011) for the first time plant extracts linkages aFormat (not all items present in each case), hydrolysis method, MALDI method (matrix), other techniques. as it requires the determination of the sites of attachment of spectrum showed peaks separated by the mass of hexose N- (attached to asparagine in a Asn-Aaa-Thr(Ser) consensus residues but the attachment site on the protein was not sequence) and/or O- (attached to Ser or Thr) linked glycans, determined (Yu et al., 2012e). MALDI-TOF analysis of solvent together with the extent of occupancy of each site and the extracts of pollen from various species followed by analysis by structures of the attached glycans. Any one site may be occupied multivariate statistics has been used as a classification method by over one hundred structures. Glycoproteins may be examined (Krause et al., 2012). Extracts gave groups of peaks in the region intact, although this rarely provides detailed information but, of 10 kDa with spacings indicating the presence of hexose more commonly, they are hydrolyzed to glycopeptides or the residues. In another investigation of plant immune responses glycans are released and analyzed separately. A large number induced by flagellin from the Gram-negative phytopathogenic of methods have been developed but, as pointed out in the bacterium Acidovorax avenae, MALDI MS using glycosyltrans- previous review of this series, many methods still lead to ferase-deficient mutants showed that 1600- and 2150-Da erroneous results. glycans were present on two flagellins (from N1141 and K1 strains), respectively. The masses measured from the un- 1. Studies on Intact Glycoproteins glycosylated flagellins agreed with the theoretical masses of around 51 kDa (Hirai et al., 2011). In another example, doublet Papers simply recording the masses of glycoproteins are not bands by HPLC with MALDI masses of 29,213 and 30,270 Da included. However, MALDI has been used by several inves- for KLK13 (kallikrein-related peptidase) corresponded to tigators to show the existence of glycosylation on proteins but glycosylation with approximately 6 sugar units (Andrade et al., without further analysis of the glycans. Thus, for example, 2011). several important glycoproteins have been identified in the proteomes of Arabidopsis thaliana and Hordeum vulgare a. Extraction and concentration of glycoproteins (barley) with the aid of lectin affinity chromatography, gel A large number of methods have been published on procedures electrophoresis, and MALDI-TOF MS (Lastovickova, for extraction and concentration of glycoproteins from protein– Smetalova, & Bobalova, 2011). Extracellular solute-binding glycoprotein mixtures. These rely on a number of differential protein (CbpB/cthe 1020) from Clostridium thermocellum has properties of the glycoproteins such as their binding to lectins or been shown to be a glycoprotein following MALDI-TOF/TOF to boronate-containing matrices. Many are listed in Table 10 MS/MS analysis of a trypsin:pronase digest. The MS/MS with a few exemplary examples discussed below.

Mass Spectrometry Reviews DOI 10.1002/mas 29 & HARVEY

TABLE 8. Use of MALDI MS for examination of carbohydrate polymers from lower organisms Species Carbohydrate Techniquesa Notes Reference Arthrobacter Determination of the optimal (Seo & Shin, crystallopoietes Trehalose TOF conditions for trehalose 2011) N-08 production TOF (DHB), Aspergillus Galactosamino- Structural determination, (Fontaine et GLC, GC/MS, fumigatus galactan immunosuppressive properties al., 2011) NMR EPS (linear -D- TOF (DHB, Analysis of biofilm formed on Aureobascidium glucan, maltotriose (Hasan et al., CHCA, an aluminium strip immersed in pullulans units connected by 2011) sinapinic), ESI sea water a (1 6) linkage Two polysaccharides Bacillus cereus Secondary cell wall R-TOF/TOF synthesised. One is constant and (Candela et al., ATCC 14579 polysaccharides (DHB) the other regulated by growth 2011) conditions Bacillus cereus, Structure determination. Similar Secondary cell wall R-TOF/TOF (s- (Forsberg et G9241, 03BB87 to glycans from B. anthracis polysaccharides DHB), NMR al., 2011a) and 03BB102 (cause fatal pneumonia) Bacillus R-TOF/TOF Isolation and structural (Singh et al., EPS licheniformis (CHCA) determination 2011a) Bacillus Structural determination of (Song et al., EPS TOF, FT-IR licheniformis glycan isolated from Kimchi 2011f) Bacillus TOF (DHB), FT- Structural determination, (Chowdhury et megaterium EPS IR, X-ray, HPLC emulsifying properties al., 2011c) RB-05 Bacillus Jute found to be an effective (Chowdhury et megaterium EPS R-TOF (DHB) fermentation substrate for EPS al., 2011b) RB-05 production Characterization (Glc, Man, Xyl, Bacillus pumilus TFA hydrolysis, (Chowdhury et EPS Ara, GlcNAc) and emulsifying UW-02 TOF (DHB) al., 2011a) properties from soil (Choma & Bradyrhizobium TOF (DHB), Three species. Glucans with 10- Cyclic- -glucans Komaniecka, spp. GC/MS, NMR 13 Glc residues 2011) Brucella Structure confirmation. Cyclic -1,2-Cyclic (Martirosyan melitensis 16 M, TOF (DHB) glucan shown to be activator of glucan et al., 2012) B. abortus 2308 human and mouse dendritic cells Deletion of manC shown to give Corynebacterium (Mishra et al., LAM, LM, PIMs TOF a PIM- and lipoglycan-deficient glutamicum 2012b) mutant Costaria costata R-TOF/TOF, Study of composition at different (Anastyuk et Fucoidans (brown alga) ESI-Q-TOF life stages al., 2012b) Partial structural determination Biosurfactant with of a biosurfactant produced by Cronobacter (Jain et al., mono-, di-, tri- and R-TOF, GC/MS an alkaliphilic bacterium isolated sakazakii 2012a) oligo-saccharides from oil contaminated wastewater Extracellular Dunaliella salina L-, R-TOF/TOF Large polymers. MALDI-TOF (Mishra et al., polymeric (Micro alga) (CHCA) identified hexose and pentose 2011a) substances Dictyopteris Polysaccharides Structural determination. (Sokolova et polypodioides and (alginic acid, TOF Fucoidans exhibited antitumor al., 2011) Sargassum sp. fucoidan) properties Erysipelothrix Capsular TOF/TOF (Shi et al., Structural determination rhusiopathiae polysaccharide (CHCA) 2012b) Structure- and metal-dependent Poly- -1,6-N- activity of Escherichia coli PgaB (Little et al., Escherichia coli acetyl-D- R-TOF (CHCA) provides insight into the partial 2012) glucosamine de-N-acetylation of glycan Cyclic Escherichia coli Occurrence and structural (Fregolino et enterobacterial TOF (DHB) O157:H- determination al., 2012) common antigen Hizikia fusiformis R-TOF/TOF Structural determination and (Anastyuk et Fucoidan (brown alga) (arabinosazone) anti-cancer activity al., 2012c) Ganoderma Low MW -1 3- NaOH, HCl, Structural characterization and (Kao et al., lucidum Glucan TOF (DHB) antioxidative activity 2012) Iso-amyl-lyase, Structural determination and Gastrodia elata (Chen et al., Glucan TOF, GLC, anti-pancreatic cancer effects of Bl. 2011b) GC/MS, NMR oligosaccharides

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TABLE 8. (Continued) Free-radical Macromolecular complex with Hizikia fusiformis depolymerization (Mavlonov et Fucoidan bee venom melittin to reduce (brown alga) TOF/TOF al., 2011) toxicity (DHB) TOF/TOF Klebsiella sp. Mono-, di-, tri- and Partial structural determination (Jain et al., (CHCA), strain RJ-03 oligo-saccharides and biosurfactant properties 2012b) GC/MS Identification of Membrane (Kimura et al., Oligosaccharides L-TOF (DHB) oligosaccharides causing bioreactors 2012a) membrane fouling Mesophilic Screening for xylan degrading R-TOF/TOF (Van Gool et lignocellulolytic Xyloglycans enzymes in complex shake flask (DHB) al., 2011) fungi fermentation supernatants Mycobacterium (Bhamidi et Arabinans TOF (DHB) Structural analysis of cell walls leprae al., 2011) Mycobacterium marinum (strain Phenolic Acyltransferase PapA5 found to be (Chavadi et al., TOF (DHB) required for biosynthesis of cell M; ATCC BAA- glycolipids wall-associated phenolic glycolipids 2012) 535) Mycobacterium Methylmannose Study of affinities for lipids in (Liu et al., TOF (DHB) smegmatis polysaccharides aqueous solution 2012e) Mycobacterium (Bhamidi, et Arabinans TOF (DHB) Structural analysis of cell walls tuberculosis al., 2011) KOH, The ability of land plants to Physcomitrella Xylans, endoxylanase, synthesize glucuronoxylans (Kulkarni et patens (moss) and glucuronoxylans TOF (DHB), is shown to predate the evolution al., 2012b) other species ESI, NMR of tracheophytes Tichocarpus R-TOF/TOF Production and anti-cancer (Anastyuk, et crinitus (red Fucoidan (arabinosazone, activity of low molecular al., 2012c) seaweed) DHB) fragments Hydrogen production by the Chrysolaminarans thermophilic eubacterium (1 3) linked D- Thermotoga L-, R-TOF Thermotoga neapolitana from (Dipasquale et Glcp with neapolitana (DHB) storage polysaccharides of the al., 2012) branching through CO -fixing diatom Thalassiosira C-2 and C-6 2 weissflogii TOF/TOF (DHB, Tichocarpus / -Carrageenan Structural analysis by ESI and (Anastyuk et arabinosazone), crinitus (red alga) oligosaccharides MALDI al., 2011) LIFT, ESI Structural similarity with Silvetia (Anastyuk et Fucoidans R-TOF, HPLC fucoidans from Fucus babingtonii al., 2012a) evanescens Sinorhizobium Succinoglycan Use for increasing solubility of (Choi et al., TOF (DHB) meliloti monomers salicylic acid 2012a) Sinorhizobium Succinoglycan Hydrophobic interactions with (Cho et al., TOF meliloti dimers fluorescent probes 2011) Sinorhizobium Succinoglycan Use for increasing solubility of (Choi et al., TOF (DHB) meliloti dimers haloperidol 2012b) Succinoglycan TOF (DHB, Sinorhizobium Structural identification and (Kwon, et al., mono-, di- and tri- AMT, THAP), meliloti 1021 fragmentation 2011b) mers -ve -Amylase, -1,3-Glucan, shown to form a Toxoplasma zymolyase, TOF trabecular scaffold in the oocyst (Bushkin et al., gondii, and -1,3-Glucan (DHB), glycans walls of Toxoplasma and 2012) Eimeria spp. (per-Me) Eimeria Ustilago scitaminea NBRC Mannosylerythritol Production and characterization (Morita et al., TOF (CHCA) 32730 (sugarcane lipid B of the biosurfactant 2011b) smut fungus) Extracellular TOF/TOF, Vibrio Isolation and characterization. (Kavita et al., polymeric GC/MS, IR, parahaemolyticus Polymer of Ara, Gal, Glc, Man 2011) substance NMR Abattoir wastewater Exo- Investigation into the formation (Seviour et al., TOF (anaerobically polysaccharides of sludge granules 2012) treated) aFormat (not all items present in each case), hydrolysis method, MALDI method (matrix), other techniques

Mass Spectrometry Reviews DOI 10.1002/mas 31 & HARVEY

TABLE 9. Reviews and general articles on the analysis of glycoproteins Subject Citations Reference (An & Lebrilla, Structural analysis of N- and O-linked glycans by tandem mass spectrometry 80 2011) (Antonopoulos et al., Glycosylation of mouse and human immune cells 52 2011) Analysis of post-translational modification of plant glycoproteins 214 (Bond et al., 2011a) Recent advances in the MS analysis of glycoproteins: Capillary and 144 (Cortes et al., 2011) microfluidic workflows (Davis & Crispin, Low- and high-throughput structural glycoproteomics 152 2011) Tandem mass spectrometry and glycoproteins 36 (Dolashka, 2012) Titanium dioxide as chemo-affinity chromatographic sorbent of (Engholm-Keller & 106 biomolecular compounds Larsen, 2011) Biochemical and biophysical characterization of humanized IgG1 produced 83 (Ha et al., 2011b) in Pichia pastoris Mass spectrometric based sulfoglycomics of N-linked and O-linked 97 (Kenny et al., 2011) oligosaccharides (Kolarich et al., Glycomics, glycoproteomics and the immune system 33 2012) Sample preparation for glycoproteins 107 (Lam et al., 2012) Recent advances in the MS analysis of glycoproteins: Theoretical 83 (Lazar et al., 2011) considerations (Leymarie & Zaia, Use of mass spectrometry for glycan and glycopeptide structural analysis 57 2012) Capillary electrophoresis-mass spectrometry of glycans derived from 125 (Mechref, 2011) glycoconjugates Methods for analysis of sialic acids and sialylated glycans 110 (Nie et al., 2012) Automated glycan analysis - (Nishimura, 2011) Development of a fully automated glycan analytical system 12 (Nishimura, 2012) Glycopeptide enrichment and separation for protein glycosylation analysis 238 (Ongay et al., 2012) (Pabst & Altmann, Glycan analysis by modern instrumental methods 123 2011) New technologies for glycomic analysis: Toward a systematic understanding (Rakus & Mahal, 117 of the glycome 2011) (Rebecchi et al., Quantitative N-linked glycoproteomics 63 2011a) Analysis of protein complexes and post-translational modification of plant (Remmerie et al., 338 glycoproteins 2011) Analytical methods for the identification and characterization of the plant N- (Ruiz-May et al., 83 glycoproteome 2012) Glycoprotein analysis using mass spectrometry: unravelling the layers of 47 (Schiel, 2012) complexity. Application of high-throughput mass spectrometry to glycoprotein analysis 99 (Singh et al., 2011b) N-Glycoproteomics in plants: Perspectives and challenges 89 (Song et al., 2011b) Glycoproteomics in health and disease 158 (Struwe et al., 2011) General review on technologies and strategies for glycoproteomics and 130 (Tousi et al., 2011) glycomics and applications to clinical biomarker research Site analysis and structural determination of glycans in monoclonal antibody 68 biopharmaceuticals Analysis of carbohydrates (N- and O-linked) on biomedically important (Yamada & Kakehi, 284 glycoproteins 2011) Tandem mass spectrometry of tagged and permethylated polysaccharides 97 (Yang, 2012) (Yang & Zhang, Solid-phase glycan isolation for glycomics analysis 108 2012a) Hydrophilic interaction liquid chromatography for structural glycomics 60 (Zauner et al., 2011) Protein O-glycosylation analysis. Comprehensive review 154 (Zauner et al., 2012)

Recent progress in quantitative glycoproteomics 39 (Zhang et al., 2012i) Structural characterization of carbohydrates by Fourier transform tandem 146 mass spectrometry 2011)

i. Use of lectins. Catala et al. (2011) have described a the method allowed the isolation of a sub-proteome with an method for enrichment of secreted plant proteins based on extremely high proportion of proteins that are predicted to be afﬁnity chromatography using the lectin Concanavalin A (Con resident in the cell wall or secretory pathway. Amine function- A) and two-dimensional LC, together with MALDI-TOF/TOF alized monolithic spin columns have been developed and used MS for analysis of the resulting tryptic peptides. Ripe tomato as adsorbents in lectin afﬁnity chromatography. Con-A was (Solanum lycopersicum) fruit was used as the test sample and coupled by a glutardialdehyde (62) link and used for the

32 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 10. Methods for glycoprotein enrichment Column Notes Reference Use of boronate affinity capture (Bicker et al., Boronate functionalized lectins For glycoprotein identification 2011) SiMAG-Boronic acid and SiMAG- For extraction of human monoclonal antibodies from a (Borlido et al., Protein A magnetic particles CHO cell supernatant 2012) Click glycosyl phenyl glycine on (Huang et al., Three-step synthesis for glycopeptide enrichment silica beads (HILIC) 2011a) (Liang & Liu, Boronic acids For capture of cis-diols 2011) 4-Vinylphenylboronic acid-silica One-pot synthesis. Used to extract glycoproteins from (Lin et al., hybrid affinity monolithic column egg white 2011d) Prepared from 4-vinylphenylboronic acid as functional (Lin et al., Phenylboronate affinity monolith. monomer and ethylene dimethacrylate as crosslinker. 2011f) Used to capture egg white glycoproteins Magnetic nanoparticles with Synthesis. Evaluated with cellulose and ovalbumin, (Lin et al., immobilized aminophenylboronic bovine hemoglobin, bovine serum albumin and 2011c) acid lysozyme as model samples Restricted access boronate affinity (Liu et al., For capture of IgG porous monolith 2012i) Macroporous boronate affinity Use of metal-organic gel as a porogenic template for (Yang et al., monolithic column the specific capture of glycoproteins 2011b) Aminophenylboronic acid- Use demonstrated for extraction of HRP tryptic (Zhang, et al., functionalized magnetic mesoporous peptides in the presence of peptides from BSA 2011b) silica Boronic acid modified magnetic (Zhang et al., Synthesised via azide and alkyne click chemistry nanoparticles 2012g) Boronic acid-functionalized Use of chitosan modified with glycidyl methacrylate (Zou et al., 2012) chitosan polymeric nanosphere and derivatization with 3-aminophenylboronic acid Other methods For separation of glycopeptides from peptides after (Lin et al., Microcrystalline cellulose hydrolysis with trypsin 2012a) N,N-Diethyl-ammonium (DEAP) - For simplified purification of equine chorionic functionalized magnetic particles gonadotropin 2011) Glycopeptides from mixtures of glycoproteins such as 1:1 Mixture of graphite carbon and ovalbumin, fetuin, haptoglobin and glycoproteins from (Xin et al., 2012) activated charcoal human plasma. For sialylated glycoproteins. Oxidation with periodate. (Yokoyama et Biotin-streptavidin Conjugation with aminooxybiotin al., 2011) purification of ovalbumin. The novel columns were said to agglutinin (WGA), and Maackia amurensis (MA) lectin, to outperform a commercially available system (Reichelt et al., capture glycoproteins from human body fluids. A method based 2012). on protection of the lectins with their target sugars prior to coupling with the nanoprobes was used to overcome the nonspecific nature of conjugation. By use of this method, lectin OO conformation was preserved, increasing by 40% and 90% the 62, Glutardialdehyde affinity of ConA and MA lectins for glycoproteins compared with synthesis with non-protected lectins. ConA immobilized Whereas Con A binds specifically a-D-mannosyl and on the nanoprobes exhibited a fivefold increase in affinity for a-D-glucosyl residues, other lectins have different specificities fetuin and ovalbumin compared with Sepharose@ConA con- and can be used to extract different sets of glycans. Erythrina taining the same amount of immobilized lectin. The bound cristagalli lectin, for example, binds galactose with specific lectins were then used to extract glycoproteins from human activity for Gal-b-(1!4)-N-acetylglucosamine, a major epitope serum, saliva, and urine. The extracted glycoproteins were in N-glycans. Gold nanoparticles (AuNPs) have been bound digested with trypsin and analyzed by nano-HPLC MALDI- onto an ethylene dimethacrylate porous polymer monolith TOF/TOF resulting in the identification of 180 proteins, 90% of within polypropylene pipette tips using azlactone chemistry which were found to be glycosylated. and used to immobilize this lectin. It was used to separate ii. Use of boronates. Boronic acids have a strong affinity desialylated transferrin from ribonuclease B, a nongalactosy- for compounds containing cis-diol groups and are, thus, ideal for lated protein. Further specificity of the lectin-modified tips was extracting carbohydrate-containing compounds from mixtures. demonstrated with a complex mixture of non-glycosylated and The rather weak B–O bonds can easily be cleaved to release the glycosylated proteins with differing terminal sugar structures carbohydrate. (Alwael et al., 2011). Aminophenylboronic acid- (5/14) functionalized magnetic Ferreira et al. (2011b) have used magnetic nanoprobes mesoporous silica has been use to enrich glycopeptides by coated with three broad-spectrum lectins, ConA, wheat germ Zhang et al. (2011b). The silica was shown to have high

Mass Spectrometry Reviews DOI 10.1002/mas 33 & HARVEY selectivity for glycopeptides from horseradish peroxidase (PIAT), has been developed for the enrichment of sialoglyco- (HRP) in the presence of a 10-fold excess of bovine serum peptides (Cao et al., 2012). In this method, peptides were first albumin (BSA) in a tryptic digest. The authors also found that separated into 24 fractions using peptide IPG-IEF. Sialoglyco- their magnetic mesoporous silica gave better sensitivity, with a peptides were relatively concentrated in low-pH fractions of limit of detection of about 0.01 ng/mL, than that of commercial the immobilized pH strips and were captured using TiO2 aminophenylboronic acid-functionalized magnetic beads. The chromatography. The method was used to identify N-glycosyla- same material has been used to extract and identify glycopro- tion sites on rat liver glycoproteins and resulted in the identifica- teins from rat serum (Liu et al., 2012f). tion of 614 sites in 582 sialoglycopeptides within 322 Qu et al. (2012) have prepared boronic acid functional- sialoglycoproteins. ized core-shell polymer nanoparticles and used them for iv. Other methods. Zhao et al. (2011) have used the extracting 18 glycopeptides from a horseradish peroxidase customized matrix, “Click OEG-CD” (63) which was synthe- digest. This method compared favorably with the eight sized by linking b-cyclodextrin (CD, 4/6) onto the surface glycopeptides enriched by using commercially available of silica gel through an oligo(ethylene glycol) (OEG) spacer meta-aminophenylboronic acid agarose under the same via click chemistry, to concentrate tryptic glycopeptides. The conditions. Other methods using boronic acids are listed in resin was packed into a gel-loader tip and used in one of two Table 10, and advances in monolithic column-based boro- modes: reversed-phase liquid chromatography or hydrophilic nate-affinity chromatography have been reviewed by Li and interaction chromatography (HILIC). The reversed-phase meth- Liu (2012) (75 references). od exhibited remarkably higher selectivity for N-linked glyco- iii. Use of titanium dioxide. Titanium dioxide has been peptides than HILIC. As many as 22, 18, and 8 glycopeptides used by several investigators to enrich sialylated glycoproteins were detected in the glycopeptide fractions obtained from (see review by Engholm-Keller & Larsen, 2011). Thus, Wang, digests of human immunoglobulin G, horseradish peroxidase Liu, and Li (2011) have constructed microcolumns of TiO2 and bovine ribonuclease B, respectively. For human a1-acid beads in 10 mL pipette tips and used them to concentrate glycoprotein glycopeptides, more than 170 glycopeptides cover- glycopeptides from fetuin. After the glycopeptides were bound ing all the glycosylation sites were detected in the enriched to the column and washed, they were eluted with 60 mL fraction. ammonia–water, pH 11, with a centrifugal spin at 80g for An indirect approach developed by Wang et al. (2012g) 30 min, and then with 10 mL of 30% acetonitrile with a spin for for glycoprotein enrichment involved growing organisms in 10 min. Two milliliters of formic acid was added to acidify the cell culture in the presence of an acetylated azido sugar. This elution which was then lyophilized for C18 reversed phase method produced glycans that had incorporated the azido group, column purification prior to MALDI-MS analysis. Zhang et al. which could then be used as an anchor for binding to, for (2011a) have extended the method to include C18 packed into a example, magnetic silica particles modified with a group GELoader Tip (Eppendorf, available from most scientific containing a disulfide and a terminal alkyne. The covalently suppliers) for fractionation of peptides and glycopeptides before bound glycopeptides could then be washed and the glycopeptide the TiO2 column, also packed into a GELoader Tip. Compared released by reductive cleavage of the disulfide bond with with the single TiO2 enrichment, sequential C18 fractionation dithiothreitol. and TiO2 enrichment produced more glycopeptides than TiO2 Silver-coated magnetic nanoarchitectures were used by Ma alone. Thus, whereas no glycopeptide signals were observed et al. (2012) to enrich glycopeptides from rat serum samples. from a mixture of human serum albumin (HSA) and IgG digests The method makes use of the reversible reaction between silver following C18 desalting, 13 were observed after the combined and glycans to selectively extract the glycoproteins from technique. Practical details for enrichment of sialic acid- mixtures. The composite microspheres were constructed with a containing glycopeptides using titanium dioxide have been high-magnetic-response magnetic colloid nanocrystal cluster described by Palmisano, Lendal, and Larsen (2011). core, a poly(methacrylic acid) interim layer and a Ag-NPs A new method, termed peptide immobilized pH gradient functional shell with high coverage. By using these particles, isoelectric focusing (IPG-IEF) assisted TiO2 chromatography only 1 min was needed for glycopeptide enrichment.

N N OEt O O N (OH)6 SiO2 Si N O O 4 NN

(OH)14 63, Click OEG-CD

34 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Among other nanoparticles used to enrich glycoproteins are from lung cancer patients. The results agreed well with those hybrid Fe3O4@SiO2@PEG-maltose magnetic nanoparticles from whole serum. (Xiong et al., 2012) used for HRP, IgG, and a1-acid-glycopro- v. Related methods for peptide analysis. Ultra-small gold tein (AGP). Kuo et al. (2012a) have used amine-derivatized nanoparticles functionalized with hydrazide groups have been Fe3O4 magnetic nanoparticles, combined with in situ peptide N- used to recover tryptic glycopeptides from biological matrices glycosidase F digestion of tryptic digests to concentrate the for peptide identification (Tran et al., 2012b). The N-glycans glycopeptides. The washed nanoparticles were either mixed were oxidized with periodate and bound to the nanoparticles. directly with the CHCA matrix or removed by repeated Peptides were then released with PNGase F. The use of a sonication in 10 mL of 50% acetonitrile/2% NH4OH. N-glycans hydrazide resin for glycoprotein capture has been reported by were also released with PNGase F and examined by MALDI- Ishihara et al. (2011) to be more efficient than lectin affinity TOF MS from either CHCA or DHB. The method was tested capture. In their method for biomarker discovery, glycoproteins with fetuin, asialofetuin, erythropoietin (EPO), and glycopep- from human plasma were oxidized with periodate and mixed tides from of mouse uterine luminal fluid. with a hydrazide resin. The captured glycoproteins were An integrated sample pretreatment system, composed of a digested with trypsin and glycans were released by PNGase F click maltose HILIC column (Yu et al., 2009), a strong cation digestion. Identification was done by MALDI-TOF MS. The exchange precolumn, and a PNGase F immobilized enzymatic method had a dynamic range of 102–106 pg/mL and was used to reactor, has been developed for simultaneous glycopeptide identify biomarkers of hepatocellular carcinoma. enrichment and online deglycosylation for identification of N-linked glycosylation sites. Analysis was done by MALDI- b. Cleanup of glycoproteins and glycopeptides TOF and nano-RP-LC-ESI-MS/MS. In model experiments, A filter-aided sample preparation method has been developed avidin was deglycosylated in the presence of 50 times its mass that allows gel-free processing of biological samples solubilized of BSA and could be detected from amounts as low as 5 fmol. with detergents for proteomic analysis. Detergents were re- Sample pre-treatment time was only about 1 hr. The method was moved by ultrafiltration and several filtration devices were successfully applied to the analysis of the soluble fraction evaluated. Microcon (Millipore, Bedford, MA) and Vivacon extracted from rat brain where 120 unique glycoprotein groups (Sartorius Stedim Biotech, various sites) filtration units with and 196 N-linked glycosylation sites were identified by nominal molecular weight cutoffs of 30,000 and 50,000 (30 and nano-RP-LC-ESI-MS/MS. 50 k, respectively) were found to be equally suitable, whereas Ozohanics et al. (2012) have compared three methods for Microcon 30 k units were more appropriate for mapping of enrichment of glycoproteins from human plasma using either N-glycosylation sites. Thus, use of filters with these relatively the glycoproteins or derived tryptic peptides. All three enrich- large cutoffs was found to facilitate depletion of detergents ment methods were based on solution-phase solid-phase extrac- (Wisniewski, Zielinska, & Mann, 2011). tion (SPE) which are more appropriately coupled with analysis The use of the hydrophilic interaction chromatography techniques such as HPLC/MS or MALDI than gel-based (HILIC)-based material named click maltose has been evaluated methods. The methods were phenylboronic acid binding of for cleanup of glycopeptides derived from the glycoproteins vicinal OH groups, WGA lectin, which binds neuraminic acids HRP, IgG, bovine RNase B, and AGP. Performance was and a strong anion exchange material which binds acidic groups. compared with that from AQ C18 (Sunchrom, Friedrichsdorf, Although several other lectins (such as Con A) are available, Germany), Empore C18 (3M, St Paul, MN), and ZipTip C18 they were deemed to be outside the scope of the work. The (Millipore, Bedford, MA). Click maltose exhibited better authors concluded that enrichment at the peptide level was more performance than the other three C18 materials for both number efficient than at the protein level and that the use of strong anion of targeted glycopeptides and their corresponding intensities. In exchange and boronic acid filled SPE cartridges gave the best addition, accurate glycopeptide profiling was achieved with enrichment. click maltose desalting regardless of peptide lengths and glycan pH Multi-modal hydrophobic interaction chromatography types (Li et al., 2011c). has been investigated as a method for separating glycosylated from non-glycosylated proteins with ribonuclease, invertase and 2. N-Linked Glycans IgG as model glycoproteins (Kallberg, Becker, & Bulow,€ 2011). The chromatographic media showed strong responsiveness to a. Identification of glycosites small variations in pH, which made it possible to fine-tune the N-linked glycosylation site analysis is frequently performed by chromatographic conditions to match the properties of the protein monitoring the Asn to Asp transition that accompanies glycan isolated. Optimal glycoprotein separations were obtained at pH 4. release by PNGase F. This conversion has been used, for Rather than extracting glycoproteins from mixtures, other example, to show that cathepsin V is glycosylated at Asn221 and investigators have taken the opposite approach and developed Asn292 (Niwa et al., 2012). However, Palmisano et al. (2012) methods for removing the proteins. Thus, Svoboda et al. (2012) have shown that this reaction can lead to false positives have developed a method for depleting human serum samples of following their observation of spontaneous Asn deamidation in the major antibody, IgG, so that glycosylation of the less E. coli proteins, even when accompanied by 18O-labeling. E. abundant immunoglobulins could be studied. A column contain- coli was chosen because this organism lacks the machinery for ing Protein G immobilized on macroporous silica was used for N-glycosylation. Tryptic digests and mock PNGase-glycan the depletion and the other IgGs were recovered with a similar release were performed and Asn deamidation was noted both Protein L column. Permethylated N-glycans, released with before and after PNGase treatment. Deamidation was especially PNGase F, could be examined by MALDI-TOF (DHB) from as noticeable with asparagines in close proximity to a glycine little as 3 mL of serum and the method was used to study glycans residue or other small amino acid.

Mass Spectrometry Reviews DOI 10.1002/mas 35 & HARVEY

Zhang et al. (2011i) have digested the total protein fraction amino acids in the peptide was necessary for satisfactory of rat liver tissue with trypsin, enriched high-mannose, and MALDI analysis. hybrid glycopeptides with Con A affinity chromatography and then removed the glycans with either Endo H or PNGase F. A b. Release of glycans total of 1063 unique N-glycosites were identified by nano-liquid N-Glycans can be released from glycoproteins chemically, chromatography tandem mass spectrometry, of which 53.0% usually with hydrazine, or enzymatically. Use of hydrazine were unknown in the Swiss-Prot database. Endo H provided a release has fallen dramatically and most investigators now use more confident assignment of the sites but a smaller dataset endoglycosidases of which there are an increasing number with compared with PNGase F, showing the complementary nature of different specificities. PNGase F is the most commonly used the two N-glycosite assignment methods. enzyme for releasing N-glycans. It cleaves the entire glycan In the approach taken by Chen et al. (2011e), proteins were from the Asn residue and shows broad substrate specificity in first digested with Lys-C into relatively large peptides and the that it releases most high-mannose, hybrid, and complex glycopeptides were selectively captured with a hydrazide resin glycans. Exceptions are those glycans carrying a fucose at the after the glycans had been oxidized with periodate. Trypsin was 3-position of the core GlcNAc residue. Typically, reduced then used to release non-glycosylated peptides leaving the glycoproteins are incubated at 378C with the enzyme overnight. glycosylated peptides attached to the resin. These glycopeptides However, Zhou et al. (2012a) have shown that glycoproteins can were subsequently deglycosylated with PNGase F for mass be completely deglycosylated in 20 min by use of a domestic spectral identification. The approach was applied to cell lysate microwave oven. (293T cells) after positive validation by a model glycoprotein A novel online enzyme reactor incorporating PNGase F on and 143 N-glycoproteins were identified. a monolithic polymer support has been developed to allow the In a study of the crystal structure and role of glycans in the rapid simultaneous release of both neutral and acidic N-glycans neuronal leucine-rich repeat protein, AMIGO-1, each of (Jmeian, Hammad, & Mechref, 2012). The reactor was con- the glycosylation sites was mutated independently to Ala, the structed in a fused silica capillary using glycidyl methacrylate- mutant proteins were expressed in HEK293 cells, and the co-ethylene dimethacrylate polymer and its activity was shown change in molecular mass was observed by sodium dodecyl to remain stable after 1 month of continuous use. Analysis was sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The performed by LC/MS. Optimum conditions for glycan release results showed that all the sites were at least partially glycosy- were attained at room temperature using a loading flow rate of lated, while MALDI-TOF analysis of trypsinated AMIGO-1 2 mL/min and a reaction time of 6 min. The method was sensitive identified un-glycosylated peptides containing Asn72 and Asn315 with as little as 100 fmol of glycoprotein and 0.1 mL of human showing that these sites were not glycosylated (Kajander et al., blood serum being needed for analysis. Model glycoproteins 2011). used to evaluate the device included RNase B, fetuin, AGP, IgG, To ensure that all glycosylation sites in a glycoprotein are and thyroglobulin. detected it is important to obtain complete sequence coverage of A recently identified endo-b-N-acetylglucosaminidase the protein. To maximize coverage, Rebecchi et al. (2011b) re- (Endo Tv) from a commercial Trichoderma viride chitinase examined conditions for tryptic digests in terms of the relative mixture has been shown to release only high mannose N-linked merits of such factors as denaturing agents (urea and Rapigest oligosaccharides such as those from RNase B, ovalbumin, and SF, Waters Corp., Milford, MA), reducing agents (dithiothreitol yeast invertase (Gerlach et al., 2012). The enzyme cleaves [DTT, 64] and tris(2-carboxyethyl) phosphine [TCEP]), and of between the GlcNAc residues of the core. A similar endo- various concentrations of alkylating agent, iodoacetamide glycosidase is endo D from Streptococcus pneumoniae which (IAM) with human apo-transferrin as a model glycoprotein. The specifically releases the glycans from the Fc region of IgG best conditions were found to be the use of 6 M urea for (Fan et al., 2012). Endo S from Streptococcus pyogenes has denaturation, 5 mM TCEP for reduction, 10 mM IAM for been shown to release only complex glycans from this source alkylation, and 10 mM DTT, to quench excess IAM before the (Baruah et al., 2012) but not those carrying a bisecting GlcNAc addition of trypsin. This method was applied to a novel residue (Goodfellow et al., 2012). Another relatively new recombinant protein, human lysyl oxidase-like 2, where two endoglycosidase is endoBI-1 from Bifidobacterium infantis glycosylation sites were detected. Yu, Luo, and Yang (2011) ATCC 15697. This enzyme has been shown to cleave the have used Proteinase K to cleave glycoproteins, exemplified by chitobiose core of high-mannose and complex N-glycans, includ- ribonuclease B, into small glycopeptides and claimed that this ing those with a bisecting GlcNAc, from several glycoproteins method is superior to the use of trypsin in a similar context. leaving the terminal GlcNAc residue with any linked fucose OH attached to the protein (Garrido et al., 2012). These activities indicate that this enzyme has possibly the broadest activity of any SH HS of this set of endoglycosidases discovered to date. Cook et al. (2012) have evaluated a commercial kit (Rapid OH Deglycosylation Kit from Prozyme, Hayward, CA) and found 64, Dithiothreitol that it reduced sample preparation time from several days to 3.5 hr. The method involved diluting the antibody with water, An LC/MS study on N-linked glycosylation of b2-glyco- adding an equal volume of denaturant and incubating at room protein I (Kondo & Østerlund, 2011) successfully identified temperature for 5 min. After this time, the solution was placed in glycans on four chymotryptic peptides whereas MALDI failed a deglycosylation unit and centrifuged (2 min at 14,000 rpm) to at one site. The authors concluded that the presence of basic bind the antibody to the membrane. The membrane was treated

36 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & with digestion buffer and the glycans were removed by In a procedure designed for high-throughput N-glycan incubation with PNGase F for 1 hr at 458C. The glycans were analysis, Zhu et al. (2012a) have employed a centrifugation- isolated by centrifugation and labeled with 2-AB. assisted microreactor to combine various stages of the protein digestion and glycan release procedures. Protein digestion was c. Clean-up of released glycans accelerated by adding 80% acetonitrile and, after acidification Oxidized ordered mesoporous carbon has been used by Qin of the protein digest with TFA, the glycopeptides were enriched et al. (2011) to clean N-glycans in a rapid method for glycan with HILIC beads. Finally, the enriched glycopeptides were profiling. The mesoporous carbon matrix was prepared by eluted and deglycosylated with PNGase F in 20 mM NH4HCO3. heating mesoporous silica with sucrose and sulfuric acid, The whole procedure could be completed within 1.5 hr. It was carbonizing at 9008C, removing the silica with HF, and applied to the analysis of N-glycans from human IgG and oxidizing with nitric acid. Concentration of the N-glycans relied chicken avidin where detection limits were found to be better on a combination of the size-exclusive effect of mesopore than analyses by more conventional methods. Analyses of against proteins as well as the interaction between glycans and glycans from human serum glycoproteins could be accom- carbon. The carbon was used to clean N-linked glycans released plished with serum volumes of less than 1 mL. with PNGase F from ovalbumin and to examine complex serum Practical details of another method published in the samples where 32 N-linked glycans could be profiled. Five of Methods in Molecular Biology series (Ruhaak et al., 2012) again these, including four core-fucosylated glycans, were found to be involves PNGase F release but the glycans were labeled with potential biomarkers for liver cancer. 2-AA. This procedure lends itself to analysis by HPLC and CE Cellulose, in the form of filter paper, has long been used for as well as MALDI-TOF. Glycans were examined from human glycan purification. Another convenient source of cellulose is plasma glycoproteins and glycan cleanup employed hydrophilic cotton wool. Selman et al. (2011a) have used this material in interaction chromatography, which allowed separation of the micropipette tips and successfully cleaned released glycans labeled glycans from an excess of labeling reagent, proteins, from IgG, glycopeptides, and fluorescently labeled (2-AA) lipids, and salts. High-throughput was achieved by conducting glycans. Pieces of cotton wool pads (approximately 500 mg) the sample preparation in 96-well plate. were packed into 10 mL pipette tips. The cotton wool was Full experimental details have also been published of washed five times with 10 mL of water and conditioned three a method for the analysis of human plasma glycoproteins and their times with 83% acetonitrile by aspirating and dispensing the attached glycans (Wang et al., 2011g). The target low-abundance solution. For sample application to the cotton tips, 39 mLof proteins were concentrated by immunoprecipitation and removal acetonitrile was added to 8 mL of a tryptic IgG digest (corre- of albumin, IgG, IgA, transferrin, haptoglobin, and a-1-antitrypsin sponding to ca. 2 mg of IgG) or a released N-glycan sample. and separated by one-dimensional anion-exchange chromatogra- The mixture was pipetted up and down 20 times to allow phy with an eight-step salt elution. Fractions from each elution adsorption. The adsorbed glycoconjugates were washed three step were transferred onto a two-dimensional reversed-phase times with 10 mL of 83% acetonitrile containing 0.1% TFA HPLC column and the eluted compounds were digested with and eluted directly onto a MALDI plate with 2 mL of water. trypsin. MALDI mass spectrometry was performed with a The technique allowed the removal of salts, most nonglycosy- QIT-TOF and LC/MS employed an Orbitrap. lated peptides, and detergents such as SDS. The resulting A simple, small-scale, and high-throughput method for MALDI-TOF-MS glycopeptides or glycan profiles were very preparation of plant N-glycans has been developed by Matsuo repeatable with different tips (as well as reused tips), and very (2011). The method involved the extraction of soluble proteins similar profiles were obtained with different brands of cotton from leaves, pepsin digestion, release of N-glycans by PNGase wool. A, and a three-step chromatographic purification process using A technique, termed “glycoblotting,” using hydrazide- cation exchange, anion exchange, and graphitized carbon. The functionalized polymer beads for carbohydrate purification has method was used to identify N-glycans from 10-mg samples been published by Furukawa et al. (2008). Glycans, released from six different plant species and from only 2 mg of pure with PNGase F, were attached to the beads through oxime horseradish peroxidase. coupling to the reducing terminus. Abe et al. (2012a) have now An and Cipollo (2011) have used both LC/MS and examined methods for releasing the glycans from the beads MALDI-TOF MS in their method for analysis of protein to label them by reductive amination. Heating the beads with glycosylation. LC/MS was used to analyze tryptic glycopeptides 2–10% of acetic acid was found to be efficient and glycans from enriched by HILIC and released glycans were analyzed by IgG were successively released and labeled with 2-AP, 2-AB, MALDI-TOF MS after permethylation to provide semiquantita- and 2-AA. tive data on the glycan profiles. The method was validated with Among more traditional methods are the uses of porous five model N-glycoproteins bearing a wide array of glycans, graphitic carbon (Blank et al., 2011, Maszczak-Seneczko including high-mannose, complex, and hybrid subtypes and et al., 2011) and BlotGlycoH hydrazide beads (Hirose et al., with both sulfate and sialic acid groups. The conditions 2011). employed by the technique allowed quantitative detection of these fragile compounds. The method was applied to hemagglu- d. Total methods for N-glycan analysis tinin from influenza B/Malaysia/2506/2004, a component of the Many combinations of the above techniques are possible, 2006–2007 influenza vaccine. The glycoprotein was found to together with novel approaches, and a number of such combina- contain 11 glycosylation sites. Approximately 90% of the tions have been described during the review period. Some of glycans were high mannose, and 10% were complex and hybrid these are described below. types, including some that were sulfated.

Mass Spectrometry Reviews DOI 10.1002/mas 37 & HARVEY

Pompach et al. (2012) have developed a method involving with 18O. This method, termed GREOL (for glycan reducing-end digestion with trypsin or GluC and separation of the resulting 18O labeling), provided good linearity with high reproducibility glycopeptides by coupled hydrophilic interaction and nano- with a dynamic range of two orders of magnitude. Spectra reversed-phase (C18) HPLC for analysis by LC-MS. Monitoring were acquired from 16O- and 18O-labeled compounds either oxoniun ions such as m/z 204 (HexNAc) and 366 (Hex-HexNAc) individually or mixed in various ratios and the method was used was used to identify the glycopeptides. N-glycans were released to analyze changes in human serum N-glycans associated with with PNGase F and analyzed by MALDI-TOF MS. A glycan hepatocellular carcinoma. A disadvantage was the mass difference database search program, GlycoPeptideSearch, was developed of only two units meaning that, for mixed samples, subtraction of to match the N-glycopeptide MS/MS spectra with glycopeptides the second isotope peak from the 16O-sample was necessary. constructed from a user-specified set of potentially glycosylated peptides and glycans obtained from the GlycomeDB glycan f. Applications to the structural determination structure database. Application to human haptoglobin and of N-linked glycans hemopexin identified 57 distinct site-specific glycoforms in Tables 11 and 12 detail applications of MALDI MS to the the case of haptoglobin and 14 site-specific glycoforms from structural determination of N-glycans and additional informa- hemopexin. However, the software was only able to make tion can be found in the tables on medical applications (29) and structural assignments to 51% of the spectra. biopharmaceuticles (34) tha are presented in their appropriate Fukuda et al. (2011) have reduced and alkylated mouse sections. This section, therefore, will only mention some of the brain glycoproteins trypsinized them and released the glycans more novel and unusual findings. with PNGase F. The released glycans were captured by BlotGlyco beads, and sialic acids were methyl-esterified with 3- methyl-1-p-tolytriazene (6/23). Finally, the captured glycans i. N-linked glycans from mammalian species were released in derivatized form with the labeling reagent, A study of N-glycans from rat kidney during diabetes and after aoWR (65). MALDI-TOF and TOF/TOF spectra were acquired modulation of the dietary fiber has produced some very unusual in the positive-ion mode from DHB. proposed high-mannose and complex-type structures that have never been reported previously. However, the structures were O deduced from only linear MALDI-TOF MS/MS spectra of 2- O NH AA derivatives (the MS/MS method was not stated), measured H2N NH masses did not fit the deduced compositions and there was insufficient evidence to support any of the structures proposed O (Kumar, Nandini, & Salimath, 2011). Furthermore, the proposed NH2 structures appeared to be incompatible with known biosynthetic NH pathways. NH NH Hypersialylated biantennary glycans, such as 66, with sialic CH3 acid attached to the galactose and GlcNAc residues have been OO identified in serum glycoproteins from bovine, lamb, and goat (order Artiodactyla) but not from other mammals (Sumiyoshi 65, aoWR reagent et al., 2012). Yang and Zhang (2012b) have developed a method based on binding of released glycans to hydrazide magnetic beads to concentrate N-glycans from reference and serum glycoproteins. The glycoproteins were digested with trypsin and the glycans were released with PNGase F. These glycans were then bound to the hydrazide beads and the unbound material was washed away. Glycans were recovered by treatment with formic acid at 608C for 1 hr. Seventeen glycans were detected from serum glycoproteins by MALDI-TOF (DHB) after the solid-phase hydrazide procedure. e. Quantitation Stable isotopic labeling has, so far, found limited use in the ii. N-Linked glycans from non-mammalian species quantitation of N-glycans, partly because of the difficulty in High-mannose N-linked glycans containing a methyl-mannose, preparing suitable standards. Zhang et al. (2011h) have addressed thought to be 3-Me-mannose, have been found in the planarian, this problem and have prepared 18O-labeled N-glycans by releas- Dugesia japonica (Natsuka et al., 2011). Similar glycans, such ingthemfromglycoproteinswithendo-H, endo-F2, or endo-F3 in as 67, were identified by Paschinger et al. (2011), together with the presence of 18O-labeled water. This reaction leaves GlcNAc glycans containing galactosylated core fucose (68, 69). Methyl- attached to the protein and gives the glycan with one remaining mannose has also been identified in N-glycans from Haliotis reducing terminal GlcNAc residue containing the labeled oxygen. tuberculata hemocyanine together with a novel structure: Labeling efficiency was close to 100%. PNGase F, a more popular MeHex-[Fuc(1!3)]GlcNAc (Velkova et al., 2011). New high- endoglycosidase, was not suitable for this reaction because mannose-type glycans containing xylose and 6-Me-mannose the glycans are released as the glycosylamines, which then of the type 70 have been identified from the red microalga, hydrolyze in a reversible manner resulting in only partial labeling Porphyridium sp. (Levy-Ontman et al., 2011). Constituent

38 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 11. Use of MALDI MS for examination of N-glycans from speciﬁc glycoproteins Glycoprotein Type Methodsa Notes Reference Structural Trypsin, PNGase F, Q- Deinagkistrodon determination (hybrid, TOF, TOF/TOF, Acutobin acutus (snake) bi-, tri-, tetra-antennary (Lin, et al., 2011a) glycans (per-Me), venom complex). Antennae GC/MS, LC-MS/MS with (Neu5Ac)2 groups L-TOF/TOF (sinapinic) Results show no Amyloid P Human serum (Weiss et al., 2011) protein, ESI, CIEF evidence for isoforms (Zhang et al., Apolipoprotein c3 Serum or plasma TOF Analysis of glycoforms 2012j) Use of the - mannosidase I inhibitor Apo CTLA-4 Recombinant in PNGase F, TOF (DHB) kifunensine to allow (Yu et al., 2011a) homodimer CHO cells crystallization. High- mannose glycans Model compound for PNGase A, TOF development of method (An & Cipollo, Asilofetuin Fetal calf serum (DHB), LC/MS, for glycoprotein 2011) glycans (per-Me) analysis (Complex) Development of Endo-H, Endo-F2, R- quantitative method (Zhang, et al., Asilofetuin Commercial QIT-TOF, glycans based on 18O-labelling. 2011h) Complex Development of PNGase F (DHB), Avidin Chicken centrifugation-assisted (Zhu, et al., 2012a) glycans microreactor (see text) Identification of penta-, Biotinylated Campylobacter TOF/TOF (CHCA), hexa-, and (Jervis et al., 2012) peptides (in vitro) species glycopeptides heptasaccharides CNBr, PNGase F, Structural TOF/TOF (sinapinic), (Sanchez et al., Calsequestrin 1 Rabbit determination, high protein and 2012) mannose glycopeptides Structural PNGase F, TOF/TOF Human in mouse determination (High- CD44 (DHB) glycans (per- (Han et al., 2012a) myeloma cells Man, hybrid, bi-, tri- Me), LC/MS, MS/MS antennary complex) Glycans by mass Cellobiohydrolase Penicillium Trypsin, TOF difference. High- (Gao et al., 2012b) I decumbens mannose, hybrid O-Glycosylated IgA CH1 and CH3 rheumatoid factor domains of 6-19 Trypsin, TOF (DHB), (Otani et al., Mouse shown to induce IgA and 46-42 glycopeptides 2012a) deposits and IgA RF mAbs glomerulonephritis Highly-fucosylated di-, Trypsin, PNGase F, tri-, tetra-antennary (Sabatte et al., Clusterin Human semen TOF (DHB), glycans complex. Ligands for 2011) (per-Me) DC-SIGN Complex bi-, tri-, tetra- PNGase F, TOF (for Corticosteroid- antennary. N-Glycans (Sumer-Bayraktar Human serum glycoproteins), ESI (for binding globulin shown to modulate the et al., 2011) glycans) function of C-B globin Cytokinin Endo H, HPLC-offline Structural oxidase/ Maize TOF/TOF (ATT, 3- determination. High- (Franc et al., 2012) dehydrogenase 1 AQ), glycans mannose glycans Site analysis. Glycan Trypsin, PNGase F, composition. Removal Didelphis aurita Endo H, TOF/TOF DM43, DM64 of glycans did not (opossum) (CHCA) peptides, affect resistance to exoglycosidases snake venoms Structural Echinococcus Trypsin, PNGase A and determination. Bovine hydatid (Paschinger, et al., granulosus F, TOF (ATT), glycans Biantennary complex cyst fluid 2012a) antigen Ag5 (2-AP) with phosphorylcholine capping antennae

Mass Spectrometry Reviews DOI 10.1002/mas 39 & HARVEY

TABLE 11. (Continued) Stereum Determination of Endo- purpureum Endo H, TOF glycosylation status. (Ogawa et al., polygalacturonase Produced in (sinapinic, CHCA), High-mannose 2012a) IVs Aspergillus glycoprotein, glycans (Hex )GlcNAc oryzae 5-10 2 Antifungal drug itraconazole shown to Endothelial inhibit VEGFR2 Human umbilical PNGase F, TOF growth factor glycosylation, vein endothelial (DHB), glycans (per- (Nacev et al., 2011) receptor 2 trafficking, and cells Me) (VEGFR2) signalling (Complex tri- and tetra-antennary glycans) PNGase F, TOF Up-regulation of sialyl- Epidermal growth Lung cancer (DHB), glycans (per- and fucosyl-transferases (Liu et al., 2011c) factor receptor cells Me) in lung cancer cells Role of YlMPO1 gene Endoglucanase I Recombinant, in mannosyl- and cell wall Yarrowia PNGase F, glycans phosphorylation (Park et al., 2011a) mannoproteins lipolytica of N- and O-linked glycans PNGase A, TOF (2,4- Unique structure of Dictyostelium DHB/CHCA), Man GlcNAc with two (Nakagawa, et al., -Factor 5 2 discoideum exoglycosidases bisecting GlcNAcs and 2011c) glycans core fucose Study of binding between IgG with no (Ferrara et al., Fc RIII receptor Human PNGase F, TOF fucose and Fc RIII 2011) receptor. High-mannose glycans Complex (bi-, tri- PNGase F, TOF antennary). In study of Fetuin Commercial (DHB), glycans (per- fluorescent probes for (Mun et al., 2012) Me) detection of fucosylated N-glycans Model compound for PNGase A, TOF development of method (An & Cipollo, Fetuin Fetal calf serum (DHB), LC/MS, for glycoprotein 2011) glycans (per-Me) analysis (complex) Sialylated bi-, tri- PNGase F, TOF (Cl- (Selman, et al., Fetuin Bovine antennary. Evaluation CCA, CHCA, DHB) 2012) of Cl-CCA Development of glycopeptide Trypsin, R-, L- Fetuin, enrichment method Bovine TOF/TOF (CHCA), (Kuo, et al., 2012a) asialofetuin with amine- glycopeptides functionalized nanoparticles Structural PNGase F, TOF/TOF determination, High- Folate-binding Human and (Jaiswal et al., (DHB), glycans (per- mannose, hybrid, bi- protein bovine milk 2012) Me) and tri-antennary complex. High-mannose, complex (bi-, tri- PNGase F, TOF antennary). In study of -Galactosidase Commercial (DHB), glycans (per- (Mun, et al., 2012) fluorescent probes for Me) detection of fucosylated N-glycans High-mannose. In study PNGase F, TOF of fluorescent probes Glucose oxidase Commercial (DHB), glycans (per- (Mun, et al., 2012) for detection of Me) fucosylated N-glycans Glycan shield of HIV From HEK293T shown to be and human predominantly high- PNGase F, TOF/TOF (Bonomelli et al., gp120 peripheral blood mannose and (DHB), glycans 2011) mononuclear independent of cells production system or viral clade

40 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 11. (Continued) Partial enzymatic deglycosylation shown Trypsin, Endo H In HEK293T to preserves structure of (Depetris et al., gp140 trimers PNGase F, TOF, cells cleaved recombinant 2012) glycopeptides HIV-1 envelope glycoprotein trimers Glycosylation at Asn91. H1N1 Glu C, TOF/TOF High-mannose. (Jayaraman et al., Sf9 Insect cells haemagglutinin (CHCA), glycopeptides Controls binding to 2012) glycan receptors Method development Trypsin-GluC, HPLC, (see text). High- PNGase F, TOF (Pompach, et al., Haptoglobin Human mannose, hybrid, bi-, (DHB), glycans (per- 2012) tri-, tetra-antennary Me) complex glycans Investigation of the effect of multimer PNGase F (in gel), TOF Haptoglobin formation on (Boonyapranai et Human serum (DHB), glycans (per- multimers glycosylation - less al., 2011) Me) sialylation found on complex glycans Structure determination. Influenza virus PNGase A, TOF Mainly high-mannose. (An & Cipollo, Hemaglutinin (B/Malaysia/250 (DHB), LC/MS, 10% complex and 2011) 6/2004) glycans (per-Me) hybrid Dermacentor Structural and PNGase A and F, Endo marginatus functional Hemelipo- H, TOF/TOF (DHB), (Dupejova et al., glycoprotein (ornate sheep characterization. High- 2011) glycans (per-Me), ESI tick) mannose glycans Novel structures Hemocyanin Haliotis PNGase F, TOF (Velkova, et al., containing terminal Me- subunit HtH1 tuberculata (DHB), glycans, ESI 2011) Hex Trypsin-GluC, HPLC, Method development PNGase F, TOF (Pompach, et al., Hemopexin Human (see text).Complex (bi-, (DHB), glycans (per- 2012) tri-, tetra-antennary) Me) Development of rapid Horseradish Leaves TOF/TOF (DHB) method for analysis (Matsuo, 2011) peroxidase (see text) Mouse fibroblast PNGase F (in gel), TOF High-mannose, (Hayoun et al., HSP60 cells (DHB), glycans biantennary complex. 2012) Human sex PNGase F, TOF Structural (Sumer-Bayraktar hormone binding Human serum (sinapinic), LC- determination. et al., 2012) globulin MS/MS, glycans Biantennary complex -L-Iduronidase Study of the influence Human produced with ER retention PNGase A, TOF of the ER-retention in Arabidopsis (He et al., 2012b) sequence (DHB), glycans signal on N- seeds SEKDEL glycosylation As model for pH multimodal Human from PNGase F, R-TOF hydrophobic interaction (Kallberg, et al., IgG CHO or NS0 (DHB), Glycans chromatography (high- 2011) cells mannose, biantennary complex) Trypsin, PNGase F, As test compound for TOF/TOF (DHB, development of cotton (Selman, et al., IgG Human CHCA), glycans, wool tips for sample 2011a) glycopeptides purification Alterations of N- PNGase F, R-TOF, glycosylation shown to (Blomme et al., IgG Mouse TOF/TOF (DHB), be hepatocyte and not B 2011) glycans (per-Me) cell driven

Mass Spectrometry Reviews DOI 10.1002/mas 41 & HARVEY

TABLE 11. (Continued) Study of binding between IgG with no (Ferrara, et al., IgG Human PNGase F, TOF fucose and Fc RIII 2011) receptor. Complex biantennary glycans Complex, biantennary. PNGase F, TOF Commercial In study of fluorescent IgG (DHB), glycans (per- (Mun, et al., 2012) (human) probes for detection of Me) fucosylated N-glycans Development of a method for glycan PNGase F, R-TOF/TOF release from hydrazide IgG Bovine (DHB), glycans (2- (Abe, et al., 2012a) beads used for glycan AB), LC/MS capture after PNGase F- release Anti-inflammatory IgG production shown to PNGase F, TOF require functional P1 (Jones et al., IgG Mouse (DHB), glycans (per- promoter in - 2012b) Me) galactoside 2,6- sialyltransferase 1 gene To show specificity of PNGase F, TOF/TOF (Baruah, et al., IgG HEK 293S cells endo S for complex (DHB), glycans 2012) glycans Development of a quantitative, cell-line based assay to measure (Schnueriger et al., IgG NK-92 cells PNGase F, TOF ADCC activity 2011) mediated by therapeutic antibodies Development of PNGase F (DHB), IgG Human centrifugation-assisted (Zhu, et al., 2012a) glycans microreactor (see text) Study of IgG PNGase F, TOF (DHB) IgG Human glycosylation in 2298 (Pu i et al., 2011) glycans (2-AB), HPLC individuals PNGase F, TOF (DHB) Effect of glycosylation (Bowden et al., IgG1 Human glycans, Negative ion on structure 2012) MS/MS Anti-inflammatory PNGase F, R-TOF/TOF activity of IgG1 shown (Karsten et al., IgG1 Mouse (DHB), glycans (per- to be mediated by Fc 2012) Me) galactosylation Biantennary complex, PNGase F, TOF Fc-glycosylation shown (Wang et al., IgG1 B-Cells (DHB), glycans (2-AA) to be modulated by B- 2011h) cell stimuli Ident. of high-mannose glycan with -linked Expressed in (Gomathinayagam IgG1 PNGase F, TOF mannose in P. pastoris Pichia pastoris et al., 2011) engineered to produce human glycosylation Biantennary complex glycans. Sialylation PNGase F, TOF/TOF, (Otani et al., IgG3 Mouse shown to determine the glycans (aoWR) 2012b) nephritogenicity of IgG3 cryoglobulins Biantennary complex glycans. Ident. of novel Endo S, TOF/TOF antigen-specific Human and (Oefner et al., IgG Fc (DHB), glycans (per- immunoregulatory mouse 2012) Me) mechanism mediated by anti-inflammatory sialylated IgGs

42 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 11. (Continued) For conjugation of IgG to Texas red or IgG(F8) CHO cells PNGase F, TOF fluorescein via 2012) hydrazide coupling to oxidized fucose. Binding of calreticulin Trypsin, TOF/TOF shown to bind to Human IgY, IgG and IgY (DHB), glycopeptides, denatured IgG even in chicken IgY 2011) peptides the presence of large high-mannose glycans As reference for lectin Trypsin, PNGase F, enrichment of cancer- TOF/TOF (CHCA, (Drake, et al., Invertase Yeast related glycoproteins as ammonium phosphate), biomarkers (high- 2011) glycopeptides mannose) Development of quantitative method Endo-H, Endo-F2, R- (Zhang, et al., Invertase Commercial based on 18O-labelling. QIT-TOF, glycans 2011h) High-mannose, complex Structural Kallikrein-related PNGase F, TOF, (Yamakoshi et al., Pig and mouse determination, bi-, tri- peptidase 4 glycans (2-AA) 2012) antennary complex Antigens from To study binding to Kappa-5 and Trypsin, TOF, (Meevissen et al., Schistosoma host C-type lectin IPSE/a1 glycopeptides 2012) mansoni receptors Cerrena sp. Biochemical WR1 PNGase F, TOF/TOF, Laccase characterization, high- (Chen et al., 2012e) basidiomycete glycans (per-Me) mannose glycans fungus As reference for lectin Trypsin, PNGase F, enrichment of cancer- TOF/TOF (CHCA, (Drake, et al., Lactoferrin Human related glycoproteins as ammonium phosphate), 2011) biomarkers glycopeptides (biantennary complex) Complex (bi-, tri-, tetra- PNGase F, TOF/TOF antennary). Lx ligands (Graham et al., Lactoferrin Milk, neutrophils (DHB), glycans (per- cleared by C-type 2011) Me) lectins Use of Wisteria floribunda agglutinin Bovine PNGase F, QIT-TOF affinity (van Leeuwen et Lactoferrin (commercial) (DHB), glycans (2-AB) chromatography. High- al., 2012a) mannose, biantennary complex Glycans shown to PNGase F, FT-ICR exhibit dynamic (Barboza et al., Lactoferrin Human milk (DHB), glycans changes during early 2012) lactation Structural determination of N- glycans during diabetes. PNGase F, TOF, Proposal of very (Kumar, et al., Laminin Rat kidney glycans (2-AA) unusual high-mannose 2011a) type structures resulting from insufficient data (see text). Identification of site- Lectin-like Human in PNGase F, pronase, specific glycosylation. oxidized low murine myeloma QIT-TOF (DHB), Bi-, triantennary (Qian et al., 2012) density lipoprotein cell line glycans, glycopeptides complex. Antennae receptor-1 with Gal-Gal terminae Legume receptors shown to recognise Lotus japonicus PNGase A, R- rhizobial lipochitin (Broghammer et Nod factor Lotus japonicus TOF/TOF, glycans oligosaccharide signal al., 2012) receptor 5 molecules by direct binding

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TABLE 11. (Continued) Structural PNGase F, TOF determination. Three Alpha-2- Human (DHB), glycans (per- sites occupied by four (Lin et al., 2012d) macroglobulin Me), CID, ETD biantennary-type glycans Mammalian dipeptidyl Site analysis after (Cotella et al., aminopeptidase- Human TOF (CHCA), peptides deglycosylation with 2012) like protein 10 PNGase F (DPP10) Unusual Glc1- PNGase F (in-gel), Man GlcNAc glycans. Myosin light chain Toxoplasma 3 5 2 (Fauquenoy, et al., TOF (DHB), glycans, Required for trafficking 1, GAP50 gondii 2011) exoglycosidase. to inner membrane complex N-glycosylation shown Recombinant in to influence the Trypsin, L-TOF, (Losfeld et al., Nucleolin structure and self- glycopeptides GC/MS 2011) insect cells association abilities of recombinant nucleolin Model compound for PNGase A, TOF development of method (An & Cipollo, Ovalbumin Chicken (DHB), LC/MS, for glycoprotein 2011) glycans (per-Me) analysis. Method development PNGase F, TOF for 96-well plate solid- (Jeong, et al., Ovalbumin Chicken (DHB), glycans (per- phase methylation. 2012b) Me) High-Man, truncated complex, hybrid. Development of stable PNGase F, TOF/TOF isotope labelled mass (Powell & Harvey, Ovalbumin Chicken (DHB), glycans (stable tags for quantification 1996) isotope label) (see text) Structural Trypsin, PNGase F, determination. 19 (Offengenden et Ovomucin Hen egg white TOF/TOF (DHB), potential N-sites, al., 2011) LIFT, glycans (Per-Me) Truncated complex, high-mannose Development of Endo-H,endo-F2, R- (Zhang, et al., Ovomucin Chicken quantitative method QIT-TOF, glycans 2011h) based on 18O-labelling. Model compound for PNGase A, TOF development of method Ovomucoid (An & Cipollo, Commercial (DHB), LC/MS, for glycoprotein precursor 2011) glycans (per-Me) analysis. Truncated complex Experimental details of (Dewpura & PCSK9 Human TOF N-glycan analysis Mayne, 2011) Potential use of N- Seeds from PNGase A, TOF glycan profiles to Phaseolin Phaseolus (DHB), glycans (per- (Marsh et al., 2011) determine authenticity species Me) of GM crops Tropidolaemus subannulatus, Structural identification Phospholipases PNGase F, TOF/TOF, Tropidolaemus (small core-fucosylated (Tsai et al., 2012) A2 glycans (per-Me) wagleri (pit high-mannose, hybrid) vipers) Identification, tissue- Human seminal R-TOF (DHB), glycans Protein C inhibitor specific expression and (Sun et al., 2011b) plasma (per-Me) function Model compound for PNGase A, TOF development of method (An & Cipollo, Ribonuclease B Bovine pancreas (DHB), LC/MS, for glycoprotein 2011) glycans (per-Me) analysis High-mannose. In study PNGase F, TOF of fluorescent probes Ribonuclease B Commercial (DHB), glycans (per- (Mun, et al., 2012) for detection of Me) fucosylated N-glycans

44 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 11. (Continued) Use as model PNGase F, TOF/TOF compound for (DHB), glycans (Hu & Mechref, Ribonuclease B Commercial comparing analysis by (reduced, per-Me), LC- 2012) MALDI, LC -MALDI MALDI, LC-ESI and LC -ESI Most toxic of three Trypsin, TOF Ricinus isoforms due to (Sehgal et al., Ricin (sinapinic, CHCA), communis beans increased glycosylation 2011) glycopeptides (hybrid, complex) Test glycoprotein for development of Serine protease, Bothrops TOF/TOF, glycans (2- program to deduce batroxobin (viper) moojeni venom AP) 2011) structure from MS/MS data. (Complex, hybrid) Shows that isoforms do Serum amyloid P (Weiss, et al., Human plasma L-TOF, glycoprotein not exist. Changes due component (SAP) 2011) to sialylation state Human MALDI to identify (Samanta et al., Spectrin TOF (DHB), PSD erythrocytes sialic acids 2011) Structural SREC-1 determination. N-glycan Trypsin, (scavenger of Asn393 regulates lysylendopepdidase, L- receptor expressed CHO K1 cells intracellular sorting of (Sano et al., 2012) TOF (DHB), in endothelial SREC-I and N-glycan glycopeptides cells) of Asn382 controls ligand binding affinity. Thrombin- GlcNAc identified as a Thrombospondin- Trypsin, TOF/TOF (Hoffmann et al., activated fourth carbohydrate 1 (CHCA), glycopeptides 2012) platelets modification Method development PNGase F, TOF for 96-well plate solid- (Jeong, et al., Thyroglobulin Porcine (DHB), glycans (per- phase methylation. 2012b) Me) High-mannose, bi-, triantennary complex Use as model PNGase F, TOF/TOF compound for (DHB), glycans (Hu & Mechref, Thyroglobulin Commercial comparing analysis by (reduced, per-Me), LC- 2012) MALDI, LC-MALDI MALDI, LC-ESI and LC-ESI Identification of 54 bi-,

Trypsin, Q-TOF, TIMP-1 Human saliva tri- and tetra-antennary (Holten-Andersen glycopeptides complex glycans. et al., 2011) Tissue localization Mono-sialylated TOF (sinapinic), transferrin shown to (Nuevo- Transferrin Human serum glycoprotein bind Ti as well as fully al., 2011) sialylated transferrin High-mannose, bi-, tri-, tetra-antennary. Influenza virus Trimeric PNGase F, TOF/TOF Glycosylation state (de Vries et al., in HEK293T hemagglutinin (DHB), glycans (2-AA) shown to be significant 2012) cells for vaccine development Human recombinant in Comparison of systems Tumor suppressor PNGase F, MALDI, (Campomenosi et baculovirus for glycoprotein protein glycans (per-Me) al., 2011) insect cells and expression Pichia pastoris Identification of four PNGase F, TOF new high-mannose-type (Levy-Ontman, et 66-kDa cell wall Porphyridium sp. (DHB), glycans (2- glycans with 6-Me- al., 2011), (Levy- glycoprotein (red microalga) AB), ESI (-ve) mannose and xylose Ontman, 2012) (see text) Identification of new R-TOF/TOF (CHCA), Helicobacter glycoproteins and new Various peptides, LC-MS/MS (Hopf, et al., 2011) pylori attached sugars (see sugars text)

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TABLE 11. (Continued) Structural determination (High- von Willebrand PNGase F, TOF/TOF, Human plasma mannose, hybrid, di-, (Canis et al., 2012) factor glycans (Per-Me) tri-, tetra-antennary complex) Glycan is pentasaccharide with Haloarchaeal -elimination, VP4 Glc, GlcA, mannose, (Kandiba, et al., pleomorphic TOF/TOF, MS/MS sulphated GlcA and a 2012) virus, HRPV-1 (-ve) terminal 5-N-formyl legionaminic acid aFormat (not all items present): Glycan release method and/or protease, MALDI method (matrix), compounds run (derivative), other methods. monosaccharides (GlcNAc, mannose, 6-Me-mannose, and xylose) were identified by HPLC after hydrolysis but all traditional methods for glycan sequencing (HPLC, exoglycosidase digestion and positive-ion MS/MS) failed to yield meaningful data. The structures were solved by negative-on MS/MS that gave the total structures. It appears that xylose and methylmannose residues are reasonably common in lower organisms. Thus, similar xylosidated high-mannose glycans also with one or two xylose residues (e.g., 71) have been found in extracts of the unicellular flagellated parasite Trichomonas vaginalis. These compounds were also modified with phosphoethanolamine (Paschinger et al., 2012b). Biantennary complex glycans with phosphorylcholine capping the antennae have been found in Echinococcus granulosus antigen Ag5 (Paschinger, Gonzalez- Sapienza, & Wilson,2012). Large high-mannose glycans with and without b-xylose of the type 72 have also been reported from the human fungal pathogen Cryptococcus neoformans (Park et al., 2012c) and high-mannose glycans with mannosylated core fucose, methyl substitution, and several xylose residues (73, 74) have been found in the opportunistic human pathogen Acanthamoeba (Schiller et al.,2012).

Man5GlcNAc2 with core fucose and two bisecting GlcNAc residues (75) has been reported as an N-glycan from Dictyostelium discoideum (Nakagawa et al., 2011c), and new fucosylated high-mannose glycans such as 76 have been found in from chanterelle mushrooms (Cantharellus cibarius) (Grass et al., 2011). Unusually, the fucose was located on an

46 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 12. Use of MALDI MS for examination of N-glycans from intact organisms, tissues or protein mixtures Organism Source Methodsa Notes Reference PNGase A and F, TOF (DHB), HPLC, Structural determination. (Schiller, et al., Acanthamoeba Whole amoeba exoglycosidase, Novel substituted high- 2012) glycans (2-AP, per- mannose glycans (see text) Me) -N-Acetylhexosaminidases Arabidopsis Whole PNGase F, TOF HEXO1 and HEXO3 found to (Liebminger et thaliana glycoproteins (DHB) catalyse formation of al., 2011) paucimannosidic N-glycans Comparison of methods. Arabidopsis Etiolated Trypsin, TOF, Structures deduced with (Zhang et al., thaliana hypocotyls glycopeptides ProTerNyc 2011l) incorrect. 1,2-Glucosyltransferase Arabidopsis (ALG10) shown to be (Farid et al., Leaves TOF thaliana required for efficient N- 2011) glycosylation and leaf growth -N-Acetylhexosaminidases Arabidopsis HEXO1 and HEXO3 shown (Liebminger, et Leaves TOF, glycans thaliana to synthesise paucimannosidic al., 2011) N-glycans Trypsin, PNGase F, R- Structure comparison between Birds (88 TOF/TOF (CHCA), (Hirose, et al., Egg white species with emphasis on species) glycans (BOA 2011) sialic acid. See text derivatives) PNGase F, R- Study of changes in (Takimori et al., Bovine Milk and IgG TOF/TOF (DHB), glycosylation during early 2011) glycans lactation Whey PNGase A, TOF/TOF, (Sriwilaijaroen et Bovine Structural determination glycoproteins glycans (2-AP) al., 2012) Hydrazine, TOF Bovine, lamb, Hypersialylated biantennary (Sumiyoshi, et Serum (DHB), glycans (2- goat glycans in these species only. al., 2012) AP) Differ from wild-type. High- Caenorhabditis Mutant Trypsin, PNGase A, (Geyer et al., mannose (±Fuc, Me), elegans embryos TOF/TOF (ATT) 2012) paucimannosidic, hybrid Glycoproteins Hydrazine, TOF Conserved oligomeric Golgi Caenorhabditis (Struwe & from whole (DHB), glycans (per- complex shown to be elegans Reinhold, 2012) organism Me), LTQ (MSn) essential for fucosylation Increased expression of PNGase F, TOF Caenorhabditis Glycoproteins galactosylated fucose epitopes (DHB), glycans (2- (Yan et al., 2012) elegans from mutant associated with altered lectin AP), HPLC sensitivity Cantharellus cibarius PNGase A, TOF/TOF Structural determination and Whole (Grass, et al., (chanterelle (DHB), LC-ESI-MS, discovery of new fucosylated mushrooms 2011) mushroom) and glycans (2-AP) high-mannose glycans other species CHO Lec-8 Overexpression of UDP- cells Madin- GlcNAc transporter shown to Chinese hamster PNGase F, TOF/TOF (Maszczak- Darby canine partially correct and dog (DHB), glycans (2- Seneczko, et al., kidney II cells galactosylation defect caused (MDCK- AB) by UDP-Gal transporter 2011) RCAr) mutation Chlamydomonas Total extracts, High-mannose, complex and PNGase A, TOF, (Mamedov & reinhardtii membrane sialylated complex glycans (2-AB) Yusibov, 2011) (green alga) glycoproteins (confirmed by sialidase) To investigate effect of O- Glycoproteins PNGase F, R-TOF GlcNAc-ase inhibitor (Mehdy et al., CHO cells and cytosol (DHB), glycans (per- PUGNAc on free 2012) fraction Me) oligosaccharide accumulation Production of mutant cells PNGase F, TOF, (Zhang et al., CHO cells Mutant cells defective in sialylation and glycans (per-Me) 2012d) fucosylation Structural determination. PNGase F, TOF (ATT, Cryptococcus Cell wall Large high-mannose glycans (Park, et al., DHB), glycans, neoformans mannoproteins with and without 1 2- 2012c) exoglycosidase xylose

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TABLE 12. (Continued) PNGase F, TOF/TOF High-mannose, complex with Danio rerio (Vanbeselaere et ZFL cells (DHB), glycans (per- additional galactose. As (Zebrafish) al., 2012) Me), GC/MS model for human disease. Defective Golgi GDP-fucose Drosophila transporter results in N- (neurally altered PNGase A, TOF (Geisler et al., Whole flies glycans lacking 1 3- and carbohydrate (DHB), glycans 2012) 1 6-fucose on the core mutant) GlcNAc Dugesia Hydrazine, TOF/TOF Structural identification, high- (Natsuka, et al., japonica Whole worms (DHB), glycans (2- mannose, paucimannosidic, 2011) (planarian) AP) includes Me-mannose Glycoproteins PNGase A, TOF/TOF Structure determination. Dugesia (Paschinger, et from whole (DHB, ATT), glycans Galactosylated core fucose japonica al., 2011) worms (2-AP) exoglycosidase and Me-mannose residues Gallus gallus PNGase F, TOF Structural determination (bi-, Red blood (Aich et al., domesticus (DHB/Nafion), tri-, tetra-antennary complex, cells 2011) (chicken) TOF/TOF, glycans hybrid) Overexpression of Man2C1 TOF, free cytosolic (Bernon et al., Human HeLa cells leads to protein glycans (per-Me) 2011) underglycosylation PNGase F, TOF/TOF Mutations of gene encoding (Hayee et al., Human Neutrophils (DHB), glycans (perfor Glc-6-PO produced 4 2011) Me) aberrant glycosylation 4-F-GlcNAc- Peracetylated 4-fluoro- treated sLeX PNGase F, TOF/TOF glucosamine shown to reduce (Barthel et al., Human (+) T cells and (DHB), glycans (per- the content and repertoire of 2011) leukemic Me) N- and O-glycans KG1a cells Method for probing structural EA.hy926 cell PNGase F, L-, R- details of polylactosamino- line from TOF/TOF (DHB), glycan chain on N-glycans (Wang, et al., Human umbilical vein Exo- and endo- and glycoproteomic 2011k) endothelial glycosidase digestion, identification of its protein cells glycans (per-Me) carriers Mast cells, PNGase F, TOF/TOF Identification of 114 high- (North et al., Human eosinophils (DHB), glycans (per- mannose, hybrid, di-, tri- and 2012) and basophils Me) tetra-antennary glycans PNGase F, TOF/TOF Human sperm binding shown Zona pellucida (Pang et al., Human (DHB), glycans (per- to be mediated by sialyl- from oocytes 2011) Me) Lewisx oligosaccharides Conserved oligomeric Golgi PNGase F, TOF, complex shown to specifically (Pokrovskaya et Human HeLa cells glycans (per-Me) regulate maintenance of Golgi al., 2011) glycosylation machinery Embryonic Trypsin, PNGase F, R- Cell-surface glycoproteins. (Reinke et al., Human kidney 293T TOF/TOF (s-DHB), High-mannose, complex (di-, 2011) cells glycans (per-Me) tri-, tetra-antennary) Trypsin, PNGase F, Development of glycan Serum (Yang & Zhang, Human QIT-TOF (DHB), purification with magnetic glycoproteins 2012b) glycans hydrazide beads PNGase F, FT-ICR Serum (DHB), glycans, Development of glycan (Aldredge, et al., Human glycoproteins LC/MS, library 2012) exoglycosidase Development of Serum PNGase F (DHB), (Zhu, et al., Human centrifugation-assisted glycoproteins glycans 2012a) microreactor (see text) Loss of effector function PNGase F, TOF/TOF Cytolytic T shown to be accompanied by (Antonopoulos et Human (DHB), glycans (per- lymphocytes major changes in N- and O- al., 2012) Me) glycosylation Trypsin, Differential N-glycan K562 chymotrypsin, PNGase composition might be (Zhang et al., Human leukaemia cell F, TOF (DHB), associated with tumor 2012m) line glycans (per-Me) multidrug resistance

48 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 12. (Continued) PNGase F, TOF/TOF Use as model compound for Serum (DHB), glycans comparing analysis by (Hu & Mechref, Human glycoproteins (reduced, per-Me), MALDI, LC-MALDI and 2012) LC-MALDI, LC-ESI LC-ESI PNGase F, TOF, TOF/TOF (DHB, Use of metabolic inhibitors (Rillahan et al., Human HL-60 cells DBP) glycans (per- used to remodel glycome 2012) Me) Structural determination (Wang et al., Human HeLa cells TOF (high-mannose, bi-, tri-, tetra-, 2012e) penta-antennary complex) PNGase F, TOF/TOF Action of smoking and lung Blood serum (Vasseur et al., Human (DHB), glycans (per- cancer on N-glycan glycoproteins 2012) Me) composition Structural determination Membrane PNGase F, TOF/TOF (high-mannose, hybrid, bi-, proteins from (arabinosazone, BHB), (Reinke et al., Human tri- and tetra-antennary hematopoietic glycans (per-Me), 2012) complex). Varied with cell cell lines exoglycosidases line Differentiation of neurones PNGase F, TOF/TOF (Gouveia et al., Human NT2N neurons (High-mannose, bi-, tri-, tetra- (DHB), glycans 2012) antennary complex)

Pancreatic NK4a carcinoma Tumour suppressor p16I - Capan-1 cells anoikis-favouring decrease in N/O-glycan/cell surface transfected (Amano et al., Human with full- PNGase F, TOF sialylation by downregulation of enzymes in 2012b) length cDNA for tumour sialic acid biosynthesis in suppressor tandem in a pancreatic p16INK4a carcinoma model Tumor biomarker PNGase F, TOF/TOF glycoproteins in seminal Seminal (Clarke et al., Human (DHB), glycans (per- plasma of healthy males plasma 2012) Me) shown to be endogenous ligands for DC-SIGN EndoBI-1, FT-ICR Characterization of enzyme (Garrido, et al., Human Milk (DHB), glycans activity 2012) PNGase F, TOF/TOF Bi-, tri-, tetra-antennary and Hematopoietic (Reinke, et al., Human (arabinosazone), bisected glycans. Variation cell lines 2012) glycans (per-Me) with cell line High-Man, biantennary Human iPSC Hydrazine (gas-phase), complex. Evidence for 201B7 cell line (Hasehira et al., Cells TOF (DHB), glycans dynamic glycome shift on and dermal 2012) (2-AP) production of induced fibroblasts pluripotent stem cells High-mannose, hybrid, Influenza A Two viral PNGase A, TOF, (Yagi et al., complex. Dependent on host virus preparations glycans (2-AP) 2012b) cell PNGase A, TOF/TOF Detection of sialylated Ixodes ricinus Salivary (Vancova et al., (DHB), glycans (per- glycans (bi-, tri-antennary (Tick) glands 2012) Me) complex) CD98 and intercellular Hodgkin's adhesion molecule-1 found to Trypsin, PNGase F, Reed- be major carriers of (Powlesland et L-428 cells TOF/TOF (DHB), Sternberg CD15/Lewisx epitope. (bi-, al., 2011) glycans (per-Me) cells tri- and tetra-antennary complex) 1,6-Fucosyltransferase- PNGase F, TOF deficient mice shown to (Fukuda, et al., Mouse Brain (DHB), glycans (Me- exhibit schizophrenia-like 2011) ester) behaviour

Mass Spectrometry Reviews DOI 10.1002/mas 49 & HARVEY

TABLE 12. (Continued) High-mannose, bi-, tri-, tetra- PNGase F, TOF/TOF Embryonic antennary. Mannosidase 2, 1 (Wang et al., Mouse (DHB), glycans (per- stem cells deficiency associated with 2011m) Me) ricin resistance Biantennary complex. Early PNGase F, TOF/TOF T-lymphocyte activation CD4 and CD8 (Redelinghuys et Mouse (DHB), glycans (per- accompanied by switch from T-lymphocytes al., 2011) Me) N-glycolyl- to N-acetylneuraminic acid Biosynthesis of N-glycans shown to be affected by direct R-TOF (CHCA), genetic mutations in the Serum (Amano et al., Mouse glycans (BOA glycosyltransferases and by glycoproteins 2012a) derivatives) changes in metabolite availability in sugar nucleotide synthesis Development of glycopeptide Trypsin, R-, L- Uterine enrichment method with (Kuo, et al., Mouse TOF/TOF (CHCA), luminal fluid amine-functionalized 2012a) glycopeptides nanoparticles Lysosomal di-N- acetylchitobiase-deficient Liver and TOF (DHB), glycans (Persichetti et al., Mouse mouse tissues shown to kidney (per-Me) 2012) accumulate Man2GlcNAc2 and Man3GlcNAc2. Structural determination (High-mannose, bi-, tri-, tetra- Neural stem Hydrazine, (TOF), antennary). Lewis X-carrying (Yagi et al., Mouse cells glycans (2-AP) N-glycans shown to regulate 2012a) proliferation of neural stem cells via notch signalling Mycosphaerella PNGase A, TOF High-mannose glycans. (Motteram et al., graminicola Glycoproteins (DHB), glycans (per- Reduced 2-mannosylation 2011) (Fungus) Me) reduced hyphal growth Production of complex Nicotiana Pepsin, PNGase A, (Nagels et al., Leaves multiantennary N-glycans by benthamiana TOF, LC-ESI-MS 2011) genetic manipulation Soluble Pepsin, PNGase A, Paucimannosidic glycans. (Matsuo & Nicotiana glycoproteins TOF/TOF (DHB), Virus-induced gene silencing Matsumura, benthamiana from leaves glycans to delete fucose 2011) Nicotiana Decreased expression of BY2 cell line TOF (DHB), glycans (Yin et al., 2011) tabacum L. plant-specific glycoepitopes Oryza sativa Production of mutants lacking (Ozawa et al., Leaves R-TOF/TOF (DHB) (rice) 1,2-xylosyltransferase 2012) Lyophilized Structural determination Phaeodactylum PNGase A and F, TOF cellular (high-mannose) and tricornutum (DHB), glycans (2- glycoproteins characterization of GlcNAc- 2011) (diatom) AB), exoglycosidase and CHO cells transferase 1. Development of rapid method Plants Leaves TOF/TOF (DHB) (Matsuo, 2011) for analysis (see text) High levels of 2-6-Neu5Ac- PNGase A, TOF, linked to human influenza. (Sriwilaijaroen et Pig Trachea, lung glycans (2-AP) (High mannose, hybrid al., 2011) biantennary complex) Elimination of antigenic - (Choi et al., Pig Heart valves TOF galactose epitope by - 2012d) galactosidase treatment PNGase F, TOF, Validation of quantitative (Zhang et al., Rabbit Serum glycans (per-Me) LC/MS method 2012a) Histo-blood group antigens PNGase F, TOF, shown to act as attachment Rabbit Duodenum (DHB), glycans (per- factors of rabbit hemorrhagic 2011) Me) disease virus infection

50 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 12. (Continued) Free N-glycans Study of enzymology Saccharomyces from TOF (DHB), -ve ion involved in endoplasmic (Chantret et al., cerevisiae endoplasmic ESI-MS/MS reticulum-associated 2011) reticulum degradation (ERAD) High-mannose glycans, Free N-glycans Saccharomyces PNGase F, TOF, metabolism of free (Hirayama & and och1 cerevisiae glycans (2-AP) oligosaccharides facilitated in Suzuki, 2011) cells och1D mutant Paucimannosidic, bi-, tri-, tetra-antennary complex. Schistosoma PNGase A, TOF/TOF (Meevissen et al., Eggs Kappa-5 shown to be a major, mansoni (DHB), glycans 2011) uniquely glycosylated component of egg antigens Structural identification Pepsin, PNGase A and Trichomonas (high-mannose, also (Paschinger, et Whole cells F, TOF (DHB), vaginalis containing pentose and al., 2012b) glycans (2-AP), HPLC phosphoethylamine, (PE)). PNGase F, R- Structural determination (van Leeuwen et Commercial TOF/TOF (DHB), (high-mannose, hybrid, di-, al., 2012b) glycans (2-AB) tri-, tetra-antennary complex) aFormat (not all items present): Glycan release method and/or protease, MALDI method (matrix), compounds run (derivative), other methods.

antenna and not the core GlcNAc. High-mannose glycans of acutus. These glycans have the highest sialic acid density ever composition Glc1–3 Man5GlcNAc2 (77–79) from Toxoplasma identiﬁed without the presence polysialic acid chains (Lin et al., gondii have been found to lack the entire 6-antenna 2011a). (Fauquenoy et al., 2011).

A major study has been performed on the identification of N-glycans from the egg-white glycomes of 88 species of birds (63 Anseriformes and 25 Galliformes) with particular reference to the types of sialic acid present (Hirose et al., 2011). Glycans were released with PNGase F and cleaned by absorption onto BlotGlycoH beads via stable hydrazone bonds. On-bead methyl esterification of carboxyl groups in sialic acids was performed by incubation with MTT in dioxane at 608C for 1 hr. The glycans were released by a transiminization reaction with O-benzyloxyamine hydrochloride (BOA, 40) to form the O-benzyloximes and identified by MALDI-TOF/TOF MS from CHCA. The results revealed clear trends and complexity patterns as well as diversity among taxonomic groups. Galliforms and small waterfowls tended to have small, truncated glycans whereas the larger waterfowls possessed more complex glycans. It was also found in Anseriformes that Neu5Gc (5/38) and Kdn (3/24), in addition Hybrid, bi-, tri-, tetra-antennary complex glycans such as to common Neu5Ac (1/11), were expressed significantly in both 80 with antennae capped with Neu5Ac(a2!8) Neu5Ac groups N- and O-glycans of glycoproteins and glycosphingolipids. This have been reported in the venom of the snake Deinagkistrodon is the first report that Kdn exists in egg white.

Mass Spectrometry Reviews DOI 10.1002/mas 51 & HARVEY

OH OH O O O COOH O OH OH HO O HO COOH COOH HO OH NHAc O O HO OH H3C O O NH HO O HOC HO SO3H

81, N-glycan from haloarchaeal pleomorphic virus

Archaea contain N-glycans that more closely resemble the matrix. The process, in general, caused fragmentation of the O-linked glycans of higher organisms than the N-glycans of peptide chain to give intense c-, y-, and z-type ions while leaving these organisms. Thus, for example Kandiba et al. (2012) have the glycosidic bonds largely intact. In this work, 1,5-diamino- released a pentasaccharide from the NTT consensus sequence naphthalene (1/70) was used as the matrix to produce mainly c- of VP4, the major structural protein of the haloarchaeal type fragments. The method allowed ladder sequencing from both pleomorphic virus, HRPV-1. The glycan, derived from the termini to reveal the O-glycosylation sites. One limitation arose host contained glucose, glucuronic acid, mannose, sulfated from the fact that, because ions of approximately <1000 Da have glucuronic acid, and an unusual terminal 5-N-formyllegiona- to be deflected, the mass range was limited to higher mass ions, minic acid residue (81) that was thought to be important for viral typically between 1000 and 8000 Da, provided that the sequence infection. contained no disulfide bridges within this region. The method was demonstrated for the localization of O-glycosylation sites with synthetic O-glycopeptides containing the tandem repeat domain D. O-Linked Glycans of recombinant MUC1, and the natural bovine glycoproteins O-Linked glycans are often more difficult to analyze than N- asialofetuin and desialylated k-casein. Novel O-glycosylation glycans because of their more diverse structures and the lack of sites were found in the C-terminal domains of fetuin (T334)and a general enzyme for their release. b-Elimination is the most k-casein-O-glycopeptide (S154 and T156), the former site being in commonly encountered method but this has the disadvantage of conflict with the published site at T154. Practical details have been leaving the glycans without a reducing terminus for fluorescence published in the Methods in Molecular Biology series (Hanisch, or related tagging. In addition, O-glycans often occur in groups 2012). on the protein, making site analysis difficult. The use of b-elimination followed by Michael addition (BEMAD) to convert Ser and Thr to dehydroalanyl- and 83 1. Site analysis 2-aminodehydrobutyroyl (see , Scheme 5) residues, respectively, has previously been reported as a method for locating A top-down method for detecting O-linked sites has been O-linked glycosylation sites. Halfinger et al. (2011) have described by Hanisch (2011). The method is based on the ISD of developed a modified protocol involving exoglycosidase diges- intact glycoproteins induced by hydrogen radical transfer from tion and tryptic digestion to produce GalNAc-substituted

R4 R4 N N O O N N 84 OH CH CH O 3 H C R 3 H3C R3 3 3

R1O HO R NH AcHNO R2 NH O 2 O 83 85 R4 H3C R3 N O N R2 NH O OH OH OH 82 O CH R O 3 R O OH 1 HO O 1 HO AcHN AcHN

H3C N N R4 86

SCHEME 5. R1 ¼ remainder of carbohydrate; R2,R3 ¼ peptide chain; R4 ¼ alkyl.

52 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & peptides, removal of the GalNAc by b-elimination with the released glycans with 1-phenyl-3-methyl-5-pyrazolone dimethylamine, and Michael addition of 2-mercaptoethanol (PMP, 5/7) has been developed. The procedure involves heating accompanied with a small amount of dimethylamine addition. the glycoprotein with PMP in aqueous ammonia solution at The resulting peptides exhibited mass tags of 60 and 27 U, 508C for 15 hr followed by cleaning the reaction products with respectively, allowing the glycosylation sites to be determined, graphitized carbon or a C18 cartridge after removal of the even with multiple glycosylated peptides. ammonia by evaporation and the excess of PMP reagent by In a related procedure, glycans were released by solvent partition. The method was illustrated with O-glycans b-elimination with sodium hydroxide in the presence of released from porcine stomach mucin and successfully applied pyrazolone (84, Scheme 5), a reagent that forms a Michael to human plasma (Wang et al., 2011c). Practical details for addition product (85) with the amino acid and also derivatizes structural studies of mucin-type O-linked glycans have been the sugar (86). Detection of the derivatized sugar enabled published (Breloy, 2012). glycosylated sites to be differentiated from phosphorylated ones (Furukawa et al., 2011a 3. Applications of MALDI to the structural determination Overath et al. (2012) have mapped O-linked glycosylation of O-linked glycans sites using a novel biotin-cystamine tag (87). The O-glycans were removed by b-elimination and their attachment sites were Applications of MALDI to the structural determination of labeled with the tag by Michael addition. Purification of the O-linked glycans are listed in Tables 13 and 14 with only the labeled peptides was achieved with magnetic streptavidin beads. more unusual glycans mentioned here. Because phosphorylated and unmodified serine and threonine The first identification of a naturally-occurring glycoprotein residues also react in the b-elimination/Michael addition reac- with a carbohydrate (glucose) attached to cysteine has been tion, differential derivatization was performed with the tag made using sublancin from Bacillus subtilis (Oman et al., labeled with four deuterium atoms. 2011). The compound was originally thought to contain a dehydroalinine linked to cysteine. N-Acetylhexosamine has also O been found attached to cysteine in the bacteriocin, glycosin F, secreted by Lactobacillus plantarum KW30. This organism also had GlcNAc attached to Ser18 (Stepper et al., 2011). HN NH O-linked glycans from snails appear to be different from those in many other species. Stepan et al. (2012) identified NH constituent monosaccharides as GalNAc, galactose, mannose, S SH fucose, and 4-OMe-galactose. They appear to be similar to snail N-glycan structures in that they display methy-hexose O residues. 87, biotin-cystamine tag

E. Proteins Containing Both N- and O-Glycosylation 2. Release of O-linked glycans Many of the studies outlined in Tables 11, 12, 13, and 14 involve Experimental details for the release of O-glycans by b-elimina- studies where both N-and O-linked glycans have been examined. tion or hydrazinolysis, their permethylation, and analysis by Common methods in these studies are first the enzymatic MALDI-TOF MS have been published (Hulsmeier,€ Welti, & removal of the N-glycans followed by release of the O-glycans Hennet, 2011). by b-elimination. A detailed protocol for analysis of both N- and Breloy et al. (2012a) have developed a method involving O-linked glycans has been published by Jensen et al. (2012) in-gel proteolysis of the glycoprotein with pronase followed by using this approach. Glycoproteins were first immobilized on elution of the resulting peptides and glycopeptides and off-gel PVDF membranes with PNGase F being used to remove the N- reductive b-elimination. The method showed sensitivity in the glycans. After desalting with cation exchange microcolumns, low picomolar range, was claimed to be superior to some other the glycans were separated and analyzed by porous graphitized methods, and was used to examine the O-glycome of human carbon liquid chromatography-electrospray ionization tandem myoblasts and of the mouse brain O-glycoproteome. mass spectrometry. In addition, the glycans were treated with A problem with hydrazinolysis is loss of monosaccharide exoglycosidases to obtain more detailed structural information. residues from the reducing terminus by a reaction known as Analysis could also involve MALDI-TOF, particularly if the “peeling.” Kozak et al. (2012) have recently shown with bovine samples are permethylated. The authors were rather critical of fetuin and bovine submaxillary gland mucin that this side-reaction this method, particularly for the analysis of isobaric glycans. can be substantially reduced if the sample is first buffer-exchanged Also, they comment that per-methylation may not be complete with solutions of either 0.1% TFA or low-molarity (100, 50, and that it could mask the presence of naturally methylated 20, and 5 mM) EDTA. Addition of calcium chloride to fetuin glycans. The latter criticism can, however, be easily overcome before hydrazinolysis gave an increase in the amount of by using isotopically labeled MeI for the methylation. Many peeling, whereas washing with EDTA abolished this effect, MALDI analyses do not employ per-methylation, but this type suggesting a role for calcium and possibly other cations in causing of derivatization does appear to improve sensitivity, particularly the peeling. of the larger compounds. On the other hand, if sample amounts A novel one-pot procedure for the non-reductive release of are limiting, losses during the work-up stage can negate the O-linked glycans combined with simultaneous derivatization of sensitivity increase.

Mass Spectrometry Reviews DOI 10.1002/mas 53 & HARVEY

TABLE 13. Use of MALDI MS for examination of O-glycans from speciﬁc glycopeptides Glycoprotein Source Methodsa Notes Reference Trypsin, TOF, FT- Structural identification and A1S 3626 and Acinetobacter (Iwashkiw et ICR (DHB), role in virulence and biofilm A1S 3744 baumanniiand al., 2012) glycopeptides formation Trypsin, V8, TOF α-L-arabino- Glycosylation (GalNAcHex (Amore et Pleurotus ostreatus (CHCA), 1 furanosidase and GalNAcHex ) at Ser160 al., 2012) glycopeptides 2 Trypsin, R-TOF, Arabinogalactan Arabidopsis TOF/TOF, LC/MS, Structural analysis of glycans (Hijazi et al., Protein 31 thaliana GC/MS, attached to hydroxyproline 2012) glycopeptides TOF (1,5- Top-down sequencing (Hanisch, Asialofetuin Bovine diaminonaphthalene) method (see text) 2011) Analysis of glycans β-Elimination, TOF Human ovarian recognized by RP215 mAB (Lee & CΑ215 (DHB), glycans (per- cancer cell line (N-glycans not detected by Azadi, 2012) Me) MALDI but detected by ESI) TOF (1,5- Top-down sequencing (Hanisch, κ-Casein Bovine diaminonaphthalene) method (see text) 2011) β-Elimination, TOF Shown to bind to paired Human (Sun et al., Collectin 12 (s-DHB), glycans immunoglobulin-like receptor (recombinant) 2012b) (per-Me) a via sialylated glycans β-Elimination, L- Characterization of (Gebhart et DsbA1 Escherichia coli TOF (DHB), glycans exogenous bacterial al., 2012) (per-Me) oligosaccharyl-transferases Mouse Trypsin, TOF/TOF Structural determination. (Harrison et α-Dystroglycan (recombinant (CHCA), LC/MS, GalNAc- and mannose- al., 2012) HEK293T cells) glycopeptides initiated glycans. Novel GalNAcβ1– Extracellular β-Elimination, TOF 4(phospho)GlcNAc found on (Breloy et al., matrix Various (DHB), glycans (per- LacdiNAc termini of core-2- 2012b) glycoproteins Me) based glycans Virus from the sooty Simian β-Elimination, R- mangabey and rhesus (Stansell et gp120 immunodeficiency TOF/TOF (DHB), macaque shown to be al., 2011) virus glycans (per-Me) modified with O-linked glycans O-Glycosylated IgA Hinge region of 6- Trypsin, TOF (DHB), rheumatoid factor shown to (Otani, et al., 19 and 46-42 IgA Mouse glycopeptides induce IgA deposits and 2012a) RF mAbs. glomerulonephritis GlcN Acylation of histone Human (HeLa TOF, ESI-MS/MS, (Fujiki et al., Histone H2B shown to facilitate its cells) glycopeptides 2011) monoubiquitination β-Elimination, TOF, Development and application (Yagi et al., IgA Human serum QIT-TOF, glycans of multidimensional HPLC 2011) (2-AP) mapping method MUC1 tandem TOF (1,5- Top-down sequencing (Hanisch, Synthetic repeat diaminonaphthalene) method (see text) 2011) β-Elimination, Protein found to be O- Recombinant (E. (Pacharra et Neurofascin 186 TOF/TOF (DHB), mannosylated within and coli) al., 2012) glycans (per-Me) outside of the mucin domain Neuronal β-Elimination, TOF Shown to bind to paired differentiation and Human (Sun, et al., (s-DHB), glycans immunoglobulin-like receptor proliferation (recombinant) 2012b) (per-Me) a via sialylated glycans factor-1 (NPDC1) Recombinant Trypsin, QIT-TOF Structure (only to Oviduct-specific (Yang et al., human (HEK 293 (DHB, 3AQ/CHCA), composition level) and glycoprotein 2012d) cells) glycopeptides biosynthesis Meningococcal PilV shown Neisseria to potentiate N. meningitidis L-, R-TOF (CHCA), (Takahashi et PilE meningitidis Type pilus-mediated internalization glycopeptides al., 2012) IV into human endothelial and epithelial cells aFormat (not all items present): Glycan release method and/or protease, MALDI method (matrix), compounds run (derivative), other methods.

54 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 14. Use of MALDI MS for examination of O-glycans from intact organisms or tissues Organism Type Methodsa Notes Reference To investigate production of Trypsin, -elimination, sialic acids in species acid hydrolysis, TOF Branchiostoma intermediate between rdel et al., Various tissues (DHB), sialic acids belcheri vertebrates and 2012) (DMB, per-Me), LC/MS, invertebrates. Mainly on GC/MS core-1 glycans Incorporation of GalNGc CHO-K1 and TOF (DHB), GAGs (free (Bergfeld et al., Cells into glycans by feeding ldl-D cells and per-Me) 2012) GalNGc -Elimination, TOF/TOF Danio rerio Multisialylated core 1. As (Vanbeselaere, et ZFL cells (DHB), glycans (per-Me), (Zebrafish) model for human disease. al., 2012) GC/MS Mutations of gene encoding -Elimination, TOF/TOF (Hayee, et al., Human Neutrophils for Glc-6-PO produced (DHB), glycans (per-Me) 4 2011) aberrant glycosylation 4-F-GlcNAc- Peracetylated 4-fluoro- treated sLeX glucosamine shown to -Elimination, TOF/TOF (Barthel, et al., Human (+) T cells and reduce the content and (DHB), glycans (per-Me) 2011) leukemic repertoire of N- and O- KG1a cells glycans Human sperm binding -Elimination after Zona pellucida shown to be mediated by (Pang, et al., Human PNGase F, TOF/TOF x from oocytes sialyl-Lewis 2011) (DHB), glycans (per-Me) oligosaccharides Binding of monoclonal -Elimination after antibodies shown to be to (Natunen et al., Human Embryonic stem cells PNGase F, TOF, glycans Gal 1 3GlcNAc 1 3Gal 2011) 1 4GlcNAc epitope Loss of effector function Cytolytic T -Elimination, TOF/TOF shown to be accompanied (Antonopoulos, Human lymphocytes (DHB), glycans (per-Me) by major changes in N- and et al., 2012) O-glycosylation Cancer cell -Elimination, L-TOF Use of automated glycan (Yamada et al., Human line (DHB), glycans (2-AA) release (with LiOH) 2012a) -elimination, TOF, Use of metabolic inhibitors (Rillahan, et al., Human HL-60 cells TOF/TOF (DHB, DBP) used to remodel glycome 2012) glycans (per-Me) Mucins from To develop staining method (Matsuno et al., Human TOF, glycans (per-Me) bile for mucin detection 2011) -Elimination, R- High-sensitivity O-glycomic Various tissues TOF/TOF, QIT-TOF analysis of mice deficient in (Ismail et al., Mouse (stomach, (DHB, CHCA) glycans core 2 1,6-N-acetyl- 2011) colon, trachea) (per-Me), ESI, GC/MS glucosaminyltransferases Replication sarcoma and Trypsin, TOF/TOF, LC- Structural determination - (Ko et al., 2012) associated transcription MS/MS, glycopeptides presence of O-GlcNAc. herpesvirus activator Characterization of O-linked glycosylation pathway Neisseria responsible for biosynthesis (Hartley et al., Biosynthetic MALDI, glycans (2-AB) gonorrhoeae of protein glycans 2011) containing N,N - diacetylbacillosamine Neisseria Identification of diNAcBac- Pili MALDI, glycans (2-AB) Glc. Study of genetic species 2011) interactions Oculina -Elimination, R-TOF Structural determination. Glycoproteins (Coddeville et arbuscula (DHB), glycans (per-Me), Mixture of mainly small from mucus al., 2011) (coral) GC/MS, ESI sulfated glycans. For development of a Submaxillary -Elimination, TOF method for Alcian blue (Dong et al., Pig mucin (DHB), glycans (per-Me), staining of mucins on PVDF 2012) membranes

Mass Spectrometry Reviews DOI 10.1002/mas 55 & HARVEY

TABLE 14. (Continued) Histo-blood group antigens -Elimination, TOF, QIT- shown to act as attachment Rabbit Duodenum TOF (DHB), glycans factors of rabbit 2011) (per-Me) hemorrhagic disease virus infection TOF/TOF (DHB), To determine carbohydrate (Tsubokawa et Rat Colon mucin glycans binding to HCM31 antibody al., 2012) Sda tetrasaccharide Intestinal recognised by the (Tsubokawa, et Rat R-TOF/TOF (DHB) mucin monoclonal antibody al., 2012) HCM31 -Elimination, TOF, Contain GalNAc, galactose, (Stepan, et al., Snails Whole animals GC/MS, LC/MS, glycans mannose, fucose and 2012) (per-Me) methylated hexose -elimination, R- Structural determination (9 (van Leeuwen, et Commercial TOF/TOF (DHB), glycans) al., 2012b) glycans (2-AB) -Elimination, Q-TOF Vespa cabro Core types 1 and 2, Lewis X (Garenaux et al., Nests (DHB), GC/MS, NMR, (Hornet) and internal Gal-Gal motifs. 2011) glycans (per-Me) Vespula -Elimination, Q-TOF Core type 1 type extended (Garenaux, et al., germanica Nests (DHB), GC/MS, NMR, by galactose oligomers. 2011) (Wasp) glycans (per-Me) -Elimination, FT-MS Structure determination and Xenopus Egg jelly (DHB), exoglycosidase IRMPD spectra. Related to (Li et al., 2011a) borealis digests egg fertilization aFormat (not all items present): Glycan release method and/or protease, MALDI method (matrix), compounds run (derivative), other methods.

F. Other Glycosylation OH OH As well as known glycosylation of flagellin in bacteria, Hopf et al. (2011) have now shown that several other proteins H3C O COOH are glycosylated in Helicobacter pylori. The sugars were H3C released by acid hydrolysis, but their type of attachment has HO NHAc yet to be identified. They appeared to be synthesized by N pathways associated with biosynthesis of bacterial O-chains H2N from lipopolysaccharides (LPS) and contained sugars such as 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulo- 91, Leg5AmNMe7Ac sonic acid (Pse5Ac7Ac, 88) previously described on flagellins. Also present were 5-acetamidino-7-acetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic acid (Pse5Am7Ac, 89), G. Glycosaminoglycans (GAGs) 2-N-acetylbacillosamine (90), and a potential legionaminic acid Reviews on the analysis of GAGs are listed in Table 15. derivative (Leg5AmNMe7Ac, 91) which have not previously Sulfate loss is a problem with the identification of these been identified in H. pylori. compounds. Recent work (Shi et al., 2012c) has shown that the sulfates attached to nitrogen are the most labile. In addition, OH OH density functional calculations have shown that sulfate loss from a protonated site occurs more easily than from a deprotonated H3C O COOH AcHN or metal-adducted site. The loss of SO3 from N-sulfate was HO found to be energetically favored by 3–8 kcal/mol in transition NHR states relative to loss from O-sulfates. To reduce the influence

88, R = CO-CH3, 5,7-Diacetamido-3,5,7,9-tetradeoxy-L-glycero- of N-sulfate loss, the authors developed a series of chemical L-manno-nonulosonic acid (Pse5Ac7Ac) modiﬁcations to selectively replace the N-sulfates of the glucosamine with deuterated acetyl groups. 89, R = CNH-CH 3, 5-Acetimido-7-acetamido-3,5,7,9-tetradeoxy- L-glycero-L-manno-nonulosonic acid (Pse5Am7Ac) Infrared matrix-assisted laser desorption/ionization (IR- MALDI) is a “softer” ionization technique than UV-MALDI and has been used to produce clean negative-ion mass spectra of sulfated disaccharides, from heparin and chondroitin sulfate, without signiﬁcant loss of sulfate groups (Tajiri & Wada, 2011). The laser operated at 5.9 mm and the matrix was urea. The sulfur content (wt%) of chondroitin sulfate could be calculated from the m/z and the signal intensity of di- and tetra-saccharides derived from chondroitinase digestion.

56 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 15. Reviews and general articles on the analysis of glycosaminoglycans GAGs) Subject Citations Reference (Jones et al., Heparin characterization: Challenges and solutions 128 2011) Proteoglycan sequencing 109 (Li et al., 2012c) (Meany & Chan, Aberrant glycosylation associated with enzymes as cancer biomarkers (general) 97 2011) Puvirajesinghe & Bioassay and structural analysis of heparin/heparan sulphates 163 Turnbull, 2012 New methods to study the composition and structure of the extracellular matrix Schiller & 149 in natural and bioengineered tissues Huster, 2012 Modern developments in mass spectrometry of chondroitin and dermatan sulfate (Sisu et al., 84 glycosaminoglycans 2011) (Staples & Zaia, Analysis of glycosaminoglycans using mass spectrometry 137 2011a) (Staples & Zaia, Mass spectrometry in carbohydrate sequencing and binding 208 2011b) (Yang et al., Hyphenated techniques for the analysis of heparin and heparan sulfate 138 2011a)

In a comparison of the use of 9-aminoacridine (6/18) and galactose. Glycation of a-lactalbumin added up to 7 and 14 DHB for the analysis of GAGs in both positive- and negative-ion lactose or monosaccharide residues, respectively, whereas three modes, Nimptsch et al. (2012) have concluded that positive-ion and up to five sugar moieties were added by b-lactoglobulin. A spectra from DHB show the strongest signals with minimal loss partial enzymatic hydrolysis with endoproteinase AspN prior to of sulfate. MALDI-TOF analysis enabled the location of the added Chondroitin and chrondroitin-4-sulfate have been con- residues to be determined. Improved detection of glycated lysine firmed as constituents of the cell surface of the freshwater polyp residues was obtained using a-cyano-4-chlorocinnamic acid Hydra (Bottger€ et al., 2012). Samples were digested with (Cl-CCA, 12). The higher glycation of whey proteins in the chondroitinase and the resulting disaccharides were labeled with lactose-free milk system relative to normal lactose-containing the fluorophore AMAC (1/58), separated by gel electrophoresis milk reflected the higher reactivity of monosaccharides com- (30% polyacrylamide gel without SDS), and identified by pared to the parent disaccharide. reversed-phase chromatography and MALDI-MS/MS. Other A method for obtaining quantitative data on glycation applications are listed in Table 16 and papers on the synthesis of patterns of human serum albumin has been described by GAGs are listed in Table 17. Barnaby et al. (2011a). Glycated HSA samples were prepared by incubating the protein with 0–15 mmol/L of glucose at pH XV. Glycated Proteins (Non-Enzymatic 7.4 and 378C for up to 5 weeks. A control HSA sample was 16 Attachment of Sugars) digested with trypsin, Glu-C or Lys-C in O-enriched water and glycated HSA samples were digested in the presence of 18O- Reviews have been published by Liu, Ru, and Ding (2012) (140 enriched water. The samples were mixed and examined by references) on glycation as a promising method for protein MALDI-TOF MS. Lysine-199, 439, and 525 were found to be modification in food and by Oliver (2011) (151 references) on the major glycation sites, in agreement with earlier work. The glycation of milk proteins. glycation pattern was dominated by early glycation products Carulli et al. (2011) have compared glycation of the whey (e.g., fructosyl-lysine) after about 2 weeks while advanced proteins a-lactalbumin and b-lactoglobulin with lactose, and in glycation end products became more prominent at longer a model system mimicking lactose-free milk with glucose and reaction times. In another study, MALDI-TOF analysis of tryptic

TABLE 16. Use of MALDI MS for examination of glycosaminoglycans and related compounds Carbohydrate Species Techniquesa Notes Reference Human Chondroitinase, R- To monitor native and bio- Glycosaminoglycans (fibroblast TOF, PSD engineered skin al., 2012) cultures) Chondroitinase, Human cancer Automated release of GAGS (Yamada, et Glycosaminoglycans TOF (DHB), cell line from proteoglycans al., 2012a) glycans (2-AA) To check that a biotinylation (Herbert et Heparin hexasaccharide Reference TOF reaction did not alter structure al., 2012) Hyaluronan tetrasaccharide in Cerebro-spinal Hyaluronan CSF associated with self- (Wang et al., fluid (CSF) of TOF tetrasaccharide repair after chronic spinal cord 2012d) rats compression Tetrasaccharide pool MALDI (caffeic (Ozug et al., from enoxaparin sodium Commercial acid), glycans and Structural determination 2012) (low MW heparin) semicarbazone aFormat (not all items present): MALDI method (matrix), compounds run (derivative), other methods.

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TABLE 17. Use of MALDI MS for examination of the products of synthesis of glycosaminoglycans and related compounds Compounds Methodsa Notes Reference Biotinylated chondroitin For production of glycan-DNA conjugates for (Kwon et al., TOF sulfate disaccharide ultrasensitive glycan detection 2012c) CH6 and CH7 (Sobhany et al., TOF For studies in chondroitin biosynthesis oligosaccharides 2012) Disaccharides from AT-III TOF Synthesis of D-GlcA- and L-IdoA-containing (Herczeg et al., binding domain of heparin (THAP) disaccharides plus sulfonato-Me analogs 2011) Glycosaminoglycan By hydrolysis of CS4 and CS6 (Pichert et al., TOF hexasaccharide polysaccharides with hyaluronate lyase 2012) Synthesis from D-GlcN and L -ido sugars (Hung et al., Heparin oligosaccharides TOF prepared from diacetone -D-Glc 2012a) Heparan sulfate As octyl glycoside by coupling disaccharide (Takeda et al., TOF tetrasaccharide units in short steps 2012) Heparin-related di- and (Hansen et al., MALDI Synthesis from L-iduronamides tetrasaccharides 2012) Heparosan and heparin -Glycosylation by D-glucosamine-derived (Zulueta et al., MALDI analogues donors 2012) (Walvoort et al., Hyaluronan oligosaccharides MALDI Automated solid-phase synthesis 2012) Non-reducing end Synthesis of glucoronic acid-containing TOF trisaccharide of heparin trisaccharide and its methanesulfonic acid (THAP) 2012c) antithrombin-binding domain analogues Sulfonic-acid analogues of antithrombin- (Herczeg et al., TOF Synthesis and anticoagulant activity binding pentasaccharide 2012) domain of heparin aFormat (not all items present): MALDI method (matrix), derivative. “MALDI” is used when the instrument is not specified. peptides from galactose-treated HSA revealed only one of the listed in Table 20. A few of the more recent developments are five potential sites, whereas analysis by LC/ESI/MS enables all itemized below and Tables 21 and 22 list work where MALDI has five to be detected (Frost et al., 2011). The signals were greatly played a part in analysis and synthesis, respectively. enhanced following treatment with sodium borohydride. Other studies of glycated proteins by MALDI are listed in Table 18. A. Lipopolysaccharides (LPS) and Lipooligosaccharides (LOS) XVI. Peptidoglycans These compounds form the outer membranes of Gram-negative bacteria and consist of the anchoring lipid A (1/18)composedof These compounds consist of GlcNAc-MurNAc disaccharides two glucosamine residues linked to several long-chain fatty (92) cross-linked by short peptides and are usually analyzed as acids, a core carbohydrate region, and often a very long muropeptides following enzymatic digestion. Reports of the use carbohydrate, the O-chain, composed of repeating oligosaccha- of MALDI to study peptidoglycans and muropeptides are ride units. Extraction is usually with solvent mixtures such as summarized in Table 19. hot phenol:water or phenol:chloroform:petroleum ether and the molecules are frequently split into their component parts by mild OH NHAc acid hydrolysis for further structural analysis. Dephosphorylation O HO and deacylation are also common. For example, Post et al. O O O O (2012) have deacylated LPS with anhydrous hydrazine followed O by acetone precipitation and phosphate groups were removed by AcHN HO H3C treatment with 48% aqueous HF for 16–24 hr at 48C. O A new hydrolysis method for LPS uses triethylamine citrate Peptide as an agent for both disaggregation and mild hydrolysis. In particular, the method enabled the identification of fragments retaining labile substituents present in the native macromolecu- 92, Peptodoglycan lar LPS structures. The method was successfully applied to the analysis of LPS of Escherichia coli and Salmonella enterica,as XVII. Glycolipids well as more complex LPS of Actnobacillus pleuropneumoniae (Chafchaouni-Moussaoui et al., 2011). This is another large group of diverse compounds with much An improved method for recording MALDI-TOF and work being directed to analysis of LPS from bacteria, many of MALDI-TOF/TOF spectra of LOS from bacteria has been which are pathogenic, and to glycosphingolipids. Several general develop by Sturiale et al. (2011b). Approximately 1 mg of reviews on glycolipids analysis have been published; these are lyophilized LOS was added to a solution of EDTA in methanol/

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TABLE 18. Use of MALDI MS for the investigation of glycated proteins Protein/amino Sugar Methodsa Notes Reference acid Combined heat and pressure shown to R-TOF/TOF (Buckow et al., BSA Glucose significantly affect progression of (CHCA) 2011) Maillard reaction Glucose, TOF/TOF Rib-BSA shown to-induce (Kuo et al., BSA fructose, ribose (sinapinic) PC12 cell death 2012b) TOF/TOF Protein glycation shown to be a factor (da Costa et Fibrinogen Methylglyoxal (CHCA) in familial amyloidotic polyneuropathy al., 2011) No support found for theory that (Svensson et Fibrinogen Glucose TOF (CHCA) glycation interferes with acetylation by al., 2012) aspirin in diabetes Glyoxal and Monitoring of products by MALDI, CD (Pampati et al., hIgG TOF (sinapinic) methylglyoxal and UV spectroscopy 2011) Hemoglobins Analysis of non-enzymatic in vitro (Lee et al., (normal and Glucose TOF (CHCA) glycation (temperature, pH etc) 2011a) variant) R-TOF/TOF Oxidative protein modifications shown Histones H2B (Guedes et al., Glucose (CHCA, to occur more rapidly in glycated and H1 2011) sinapinic) histones in glycation region Horse heart Sugars shown to generate internal (Bokiej et al., Ribose TOF myoglobin glycation cross-links 2011) Trypsin, TOF Glycation sites at Lys 12, 233, 281/276, (Frost, et al., HSA Galactose (CHCA), 414, 525 2011) glycopeptides Lys-C, TOF (Barnaby et HSA Glucose Glycated sites found to vary with time (CHCA, DHB) al., 2011b) TOF/TOF Study of binding of monoclonal (Saito et al., HSA Glucose (sinapinic), antibodies to glycated albumin. 2011) glycoprotein Tertiary structure altered. Trypsin, Glu-C, Use of 16O/18O to quantify glycation (Barnaby, et HSA Glucose Lys-C, TOF products with time al., 2011a) (DHB/CHCA) Di-OH-acetone, Effect of concentration, time and (Seneviratne et HSA di-OH-acetone TOF (sinapinic) temperature (DHA-phosphate used in al., 2012) phosphate skin tanning preparations) Glyceraldehyde, Zn(II) shown to reduce the amount of (Seneviratne et HSA TOF (sinapinic) methylglyoxal AGE formation al., 2011) Use of ESI-IT-TOF and L-TOF. 16 (Bai et al., HSA Glucose L-TOF Sites in diabetic patient 2012) Shown to produce native-like TOF/TOF (Oliveira et al., Insulin Methylglyoxal aggregation and inhibition of fibril (CHCA) 2011) formation Asp-N, TOF Glucose, (DHAP/ NH -Lactalbumin added up to 7 and 14 - and - 4 (Carulli, et al., galactose, cit, CHCA/ mono or disaccharide respectively, - Lactalbumin 2011) lactose NH4PO4H2, Cl- lactoglobulin added 3 and 5. CCA) Maillard-type glycoconjugates from Galactose, dairy proteins shown to inhibit (Laparra et al., -Lactoglobulin L-TOF lactose adhesion of Escherichia coli to mucin. 2011) Possible use as food additives (Corzo- Study of the ability of the product to act -Lactoglobulin Galactose TOF as a foaming agent 2012) Trypsin, TOF -Lactoglobulin (CHCA), ESI, Residues Lys47 and Lys69 were found (Ferranti et al., Lactose from whey GC/MS, to be lactosylated at the time of milking 2011) glycopeptides - Glycated macroglobulin shown to form (Kong et al., 2 D-ribose TOF (sinapinic) Macroglobulin aggregates with high toxicity 2011) Lysine- TOF (sinapinic Synthesis of hetero-trimers of collagen containing (Kitamura et Glucose acid), LC- model peptides. Lysine proximity collagen model al., 2011) MS/MS shown to significantly affect glycation peptides

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TABLE 18. (Continued) Conjugation at high temperature (Sarabia-Sainz PSA Lactose TOF (120oC). Up to 41 lactose attached. et al., 2011) Recognized by bacteria. Whey proteins MALDI identification of tryptic marker R-TOF/TOF (Cucu et al., Glucose peptides that resist protein glycation (CHCA) 2012) milk during food processing L-TOF Chromatographic purification and (Bund et al., Whey proteins Dextran (CHCA) structural characterization 2012) Effect of Maillard-induced L-TOF glycosylation on the nutritional quality, (Wang & Whey protein Dextran (CHCA) solubility, thermal stability and Ismail, 2012) molecular configuration aFormat (not all items present): MALDI method (matrix), compounds run, other methods. water (1:1, v/v), vortexed, and then sonicated for 10 min. Rapid mance than CMBT, DHB, or THAP. The total time for lipid desalting was performed with a small quantity (5–10 mL) of the isolation and mass spectrometric analysis was approximately ammonium form of Dowex 50WX8-200 (Dow Chemical 10–15 min. In another method (Beceiro et al., 2011) lyophilized Company, Midland, MI) cation-exchange resin. The resin was crude cells have been incubated with iso-butyric acid-1 M placed on top of a small piece of ParafilmW (American National ammonium hydroxide (5:3, v/v) at 1008C for 2 hr, with Can, Greenwich, CT) and the excess fluid was replaced with the occasional vortexing. Samples were washed with water and same volume of the sample dispersion. Finally, the sample methanol. The resulting pellet consisting of the insoluble lipid A solution, together with the same volume of 20 mM dibasic was subsequently solubilized with chloroform–methanol–water ammonium citrate, was deposited on a thin layer of the freshly for analysis by MALDI-TOF from DHB. prepared THAP/nitrocellulose MALDI matrix that had been deposited on the MALDI target. To avoid spreading the matrix B. Glycosphingolipids (GSLs) spot over a broad area of the target, the cleaned MALDI plate was treated with commercially available POLmetal (SPI Sup- Several reviews on GSL analysis have been published; these are plies, West Chester, PA) polishing paste to provide a hydropho- listed in Table 23. These compounds are frequently analyzed bic coating. MALDI-TOF and ISD spectra were obtained. These intact but, because the lipid portion contributes considerable yielded B-type ions, corresponding to core oligosaccharide(s), heterogeniety, this is frequently removed enzymatically if and Y-type ions, which are related to lipid A unit(s). The analysis of the carbohydrate is all that is required. Separations of structure of the lipid A could be obtained directly from purified the intact molecules are frequently performed by TLC. intact LOS without the need for any chemical manipulations. a. Analysis of intact molecules Different MALDI matrices have been found to be best for different parts of these complex molecules. Thus, for example, Valdes-Gonzalez et al. (2011b) have developed a method for Casabuono et al. (2011) have found that nor-harmane (1/35) blotting glycosphingolipids onto PVDF membranes from high- was the best for lipid A whereas, for the intact molecule or performance TLC plates and analysing these directly with a oligosaccharides, THAP alone or with the addition of 20 mM MALDI-QIT-TOF instrument using DHB as the matrix. To ammonium citrate gave the best results; LPS from the plant achieve good mass spectra, the membranes were pressed with a pathogen Xanthomonas axonopodis pv. Citri was used. paper tissue to give a more uniform membrane surface and to Reviews on analyses of these compounds including analy- remove the excess of matrix crystals. The PVDF membrane was sis by MALDI have been published by Nazarenko, Crawford, attached to a MALDI sample plate with electrified double and Ivanova (2011), (LPS from marine bacteria, 173 references) adhesive tape to reduce charging of the plate. In a second paper and by De Soyza et al. (2012) (LPS structure and biological (Valdes-Gonzalez et al., 2011a), the authors report use of two- activity from the cystic fibrosis pathogens Bukholderia cepacia dimensional TLC to separate and image lipids in human brain complex). tissue. Profiles were obtained for phospho- and glyco-lipids. The results from analyses on gangliosides showed that di- and tri- sialogangliosides were richer in d20:1 sphingosine-containing a. Lipid A ceramide than were monosialogangliosides. Kawasaki (2012) has presented a short summary of lipid A Another method involving the transfer of lipids separated on analysis in a larger review of lipid A properties (127 references) a TLC-plate to a PVDF membrane (1808C for 30 sec), followed and practical details for the isolation and structural characteriza- by direct mass spectrometric analysis of the individual lipids on tion of lipid A have been published (Caroff & Novikov, 2011). the membrane by ion trap-type MALDI-TOF MS, has been Li, Wang, and Ernst (2011) have reported a new rapid and reported by Taki (2012). This technology was applied to the sensitive one-step isolation protocol for the identification of analysis of individual lipids from the human brain of patients both phospholipids and lipid A from Francisella tularensis. with Alzheimer’s disease where it was found that the levels of Lyophilized cells were suspended in 100 mL chloroform/metha- the gangliosides GD1b (25) and GT1b were lower in the nol (2:1, v/v), vortexed for 1 min, and centrifuged at 5000g for hippocampal gray matter of the patients than in the corresponding 1 min. The resulting supernatant was examined directly by tissue of patients with Parkinson’s disease or the control patients. MALDI TOF/TOF MS with nor-harmane as the matrix in An on-target desalting method has been described by Satoh negative-ion mode. This matrix was said to give better perfor- et al. (2011) for desalting the ganglioside GM1 (6/66) from

60 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 19. Use of MALDI MS for examination of bacterial peptidoglycans and muropeptides Species Peptidoglycan Methodsa Notes Reference Antibiotic empedopeptin shown to inhibit cell wall biosynthesis through Ca2+- Bacillus subtilis Peptidoglycan TOF (ATT) dependent complex formation with 2012b) peptidoglycan precursors Ibentification of enzymes acting Candida Phospho- R-TOF specifically on -mannosylation of the (Mille et al., albicans peptidomannan (DHB) phospholipomannan cell-wall 2012) glycosphingolipid Clostridium TOF Found to have high level of GlcNAc (Peltier et al., Peptidoglycan difficile (CHCA) deacetylation and mainly 3-3 cross-links 2011) Lysozyme-induced peptido-glycan N- Enterococcus TOF (Benachour et Muropeptides acetylglucosamine deacetylase PgdA faecalis (CHCA) al., 2012) shown to be required for virulence Fluorescent labelling for study of (Olrichs et al., Escherichia coli Peptidoglycan TOF biosynthesis 2011) Three redundant murein endopeptidases Escherichia colK TOF/TOF (Singh et al., Muropeptides found to catalyse an essential cleavage K12 (CHCA) 2012) step in peptidoglycan synthesis Escherichia coli, Muropeptides In situ probing of newly synthesized Agrobacterium labelled with (Kuru et al., MALDI peptidoglycan in live bacteria with tumefaciens, and fluorescent D- 2012) fluorescent D-amino acids Bacillus subtilis amino acids Peptidoglycan modifications shown to Helicobacter (Wang et al., Muropeptides TOF (DHB) confer lysozyme resistance and contribute pylori 2012b) to survival in the host Lactobacillus Characterization of O-acetylation of (Bernard et al., Peptidoglycan TOF plantarum GlcNAc 2011) Digestion Lactobacillus Ident. of key hydrolases for with (Rolain et al., plantarum Muropeptides morphogenesis, autolysis, and peptide- mutanolysin, 2012) WCFS1 glycan composition TOF Lactobacillus (Regulski et Muropeptides TOF Analysis of peptidoglycan hydrolase casei al., 2012) Characterization of the cell wall Lactobacillus (Claes et al., Muropeptides TOF hydrolase activity of the major secreted rhamnosus 2012) protein Anti-inflammatory capacity of lactobacilli Lactobacillus in experimental colitis driven by NOD2- (Fernandez et Muropeptides TOF salivarius Ls33 mediated recognition of specific al., 2011) muropeptide Showed that peptidoglycan sacculi (Slamti et al., Leptospira spp. Muropeptides TOF, ESI from retain the helical shape of intact cells 2011) O-Glycans from Pseudallescheria (Figueiredo et peptidorhamno MALDI Recognition of toll-like receptors boydii al., 2012a) mannans Characterization of a peptidoglycan- Streptococcus TOF (Caliot et al., Muropeptides anchored polysaccharide involved in cell agalactiae (CHCA) 2012) wall biogenesis LytN, a murein hydrolase in the cross- Staphylococcus TOF wall compartment shown to be involved (Frankel et al., Muropeptides aureus (CHCA) in proper bacterial growth and envelope 2011) assembly (Frankel & Staphylococcus Findings explain how murein hydrolases Muropeptides TOF Schneewind, aureus complete the bacterial cell cycle 2012) Identification of genetic determinants and UDP-Linked Staphylococcus enzymes involved with the amidation of (Figueiredo et peptidoglycan TOF aureus glutamic acid residues in the al., 2012b) precursors peptidoglycan Muropeptides Streptococcus (Bui et al., and teichioc TOF Analysis of cell wall components pneumoniae 2012) acids aFormat (not all items present): MALDI method (matrix), other methods.

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TABLE 20. Reviews and general articles on the analysis of bacterial glycolipids Subject Citations Reference (Cheng et al., Lipid and glycolipid analysis by TLC and TLC-MS 118 2011b) (Fahy et al., Lipid classification, structures and tools 45 2011) (Fuchs et al., Lipid and glycolipid analysis by TLC and TLC-MS 224 2011) Analysis of phospholipids and glycolipids by TLC and MALDI 112 (Fuchs, 2012) (Fujiwara, Distribution, characterization of mycobacterial glycolipids and host responses 93 2012) (Han et al., Multi-dimensional mass spectrometry-based shotgun lipidomics 242 2012e) canine CSF. A total of 1.5 mL of DHB solution and 1 mL of the batch-wise cation-exchange chromatography using a Waters sample were mixed thoroughly, and 1 mL of this mixture was Accell Plus CM Cartridge (Waters Corp., Milford, MA). deposited on the sample plate and dried. The sample spots were Although ESI and MALDI-TOF mass spectrometry have treated immediately before MALDI TOF MS analysis with been used extensively to characterize sphingolipids and GSLs, 2 mL of ice-cold 0.1% TFA and left for 10 sec after which time full details of the various ceramide species such as the detailed the solution was removed with a micropipette. A convenient and composition of the acyl chains, etc., are often not reported. rapid method for detergent removal from sialic acid-containing Tanala et al. (2011) have performed a systematic analysis of GSLs and neutral glycolipids has been reported (Suzuki & ceramide species, including the long-chain base with nona- Kabayama, 2012). The sample was dried in a glass tube, octadeca lengths using MALDI-TOF MS with high-energy CID followed by washing with organic solvent. Of 18 organic at 20 keV on an AXIMA (Shimadzu Biotech, Manchester, UK) solvents that were tested, dichloroethane proved to be the most “Performance” TOF/TOF instrument. General rules to discrimi- suitable and completely removed the nonionic detergent Triton nate between isomeric and isobaric ceramide species were X-100 (Dow Chemical Company, Midland, MI) and interference proposed; these rules were unrelated to the presence or absence caused by other nonionic, zwitterionic, or ionic detergents from of sugar chains. In addition, the high-energy CID generated 3,5A samples analyzed by MALDI-QIT-TOF MS. ions, indicating Hex-(1!4)-Hex linkage in the sugar chains. A method for extraction and separation of galactosyl- Using this method, the investigators demonstrated distinct differ- sphingosine (psychosine, GalSph, 93) and glucosylsphingosine ences among ceramide species, including free ceramides (3/20), (GlcSph, 93 with glucose rather than galactose) from other sphingomyelins (94), and neutral GSLs of glucosylceramides, glycosphingolipids has been described by Li et al. (2011f) using galactosylceramides, lactosylceramides, globotriaosylceramides, Krabbe disease monkey brain and Gaucher spleen as experimen- and Forssman glycolipids (GalNAc-a-(1!3)-GalNAc-b-(1!3) tal targets. Acetone was used as the solvent because it -Gal-a-(1!4)-Gal-b-(1!4)-Glc-Cer) in equine kidneys. does not extract other GSLs except for modest amounts of A rapid proﬁling method for bovine and human milk galactosylceramide, (1/74) sulfatide (6/16), and glucosylcera- gangliosides employing MALDI-FT-ICR MS with CID and mide (7/20). The positively charged GalSph or GlcSph in the infrared multiphoton dissociation (IRMPD)-induced fragmenta- acetone extract were readily separated from other GSLs by tion has been described by Lee et al. (2011d). The samples were

OH OH O NH2 HO OH O

93, Galactosylsphingosine

NH O O H2N P O O OH

94, Sphingomyelin

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TABLE 21. Use of MALDI MS for examination of bacterial lipopolysaccharides Fraction Species Methodsa Notes Reference analysed Resistance to colistin shown to be Acinetobacter TOF (DHB/citric (Beceiro, et Lipid A the result of phosphoethanolamine baumannii acid) al., 2011) addition to hepta-acyl lipid A pmrCAB operon shown to mediate Acinetobacter polymyxin resistance through (Arroyo et al., baumannii ATCC Lipid A TOF (ATT) phosphoethanolamine modification 2011) 17978 of lipid A (Chafchaouni- Actnobacillus Use of triethylamine citrate to LPS, lipid A L-TOF (DHB) Moussaoui, et pleuropneumoniae hydrolyse LPS al., 2011) Carbohydrate Structural determination. - Arcobacter backbone Glc(1 7)- -Hep-(1 5)- - (Silipo et al., R-TOF (THAP) halophilus (penta- Kdo4P-(2 6)- -GlcN4P-(1 6)- 2010) saccharide) -GlcN1P Structural determination. Unusual - Azorhizobium (Choma et al., Lipid A TOF no HO-substituted very long chain caulinodans 2012) fatty acids Identification of the human tumor- R-TOF Bacteroides ovatus specific antigen (Henderson et LPS and CPS (arabinosazone), strains D-6 and F 1 Gal 1 3GalNAc - (Thomsen al., 2011a) ESI Friedenreich) on gut bacteria Bacteroides Lipid A phosphate position shown thetaiotaomicron TOF, TOF/TOF, to determine differential host toll- (Coats et al., Lipid A and Porphyromonas (CMBT) like receptor 4 responses to related 2011) gingivalis symbiotic and pathogenic bacteria Structural study in different Bordetella (Basheer et al., Lipid A TOF (DHB) virulence phases. Palmitic acid bronchiseptica 2011) found for first time Bordetella Deep-rough LPS shown to (Sisti et al., LPS, lipid A TOF bronchiseptica modulate host immune response 2011) Lipopolysaccharide core shown to (Conde- Brucella abortus Lipid A R-TOF (DHB) act as a shield against innate immunity recognition 2012) AraN shown to be essential for Burkholderia (Hamad et al., Lipid A, core L-TOF LPS export and intrinsic cenocepacia 2012) antimicrobial peptide resistance Burkholderia Transcriptional responses to (Loutet et al., LPS TOF cenocepacia polymyxin B in isogenic strains 2011) Burkholderia TOF/TOF Development of improved MALDI (Sturiale, et LPS cenocepacia K56-2 (THAP) method al., 2011b) Burkholderia TOF (DHB), de- (Madala et al., cepacia strain ASP Lipid A Structural determination phosphorylated 2011) B 2D TOF (DHB), Structural determination. First Burkholderia mallei Capsular poly- (Heiss et al., Glycans (PMAA report on a mannan capsular and B. pseudomallei saccharide 2012) derivs.) polysaccharide in these bacteria Study of the in vitro susceptibility Burkholderia (Jassem et al., Lipid A TOF of the bacterium to vietnamiensis 2011) aminoglycosides Complex that inserts LPS into the (Freinkman et Escherichia coli Lipid A MALDI bacterial outer membrane shown to al., 2011) form a two-protein plug-and-barrel (Chafchaouni- Use of triethylamine citrate to Escherichia coli LPS, lipid A L-TOF (DHB) Moussaoui, et hydrolyse LPS al., 2011) Use of synthetic repeating unit to show WdbD catalyses addition of (Clarke et al., Escherichia coli O-Chain TOF Me-phosphate to non-reducing 2011) terminus R-TOF (Gopal et al., Escherichia coli EPS Degradation by CdS quantum dots (sinapinic, DHB) 2011) Study of phase transformations in (Faunce & Escherichia coli Lipid A TOF (sinapinic) lipid A-diphosphate initiated by Paradies, sodium hydroxide 2012)

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TABLE 21. (Continued) For synthesis of supported (Kaufmann et Escherichia coli LPS TOF lipopolysaccharide bilayers al., 2012) Structural determination and Escherichia coli (Zaccheus et O-Chain R-TOF (DHB) interaction with infecting TD2158 al., 2012) bacteriophage HK620 Escherichia coli O8 Biosynthesis of polymannose LPS (Greenfield et O-chain TOF/TOF and O9a O-antigens al., 2012) Effect of acyl chain length on (Li et al., Francisella novicida Lipid A TOF (CMBT) antibiotic resistance 2012h) Role of lipid A phosphate Francisella novicida (Kanistanon et Lipid A TOF (CMBT) modification in virulence and long- mutant al., 2012) term protective immune responses Francisella Structural determination. Three (Wang et al., LPS TOF (DHB) tularensis types of glycan identified 2011j) Francisella O-Chain Study of immunology for vaccine (Lu et al., TOF tularensis repeats development 2012) Francisella Structural determination. More (Beasley et al., tularensis (live Lipid A TOF (ATT) complex than originally believed 2011) vaccine strain) TOF/TOF Lipid A, Simultaneous analysis of lipid A (Zhou et al., Helicobacter pylori (CMBT), cardilipin and cardiolipin 2012b) MS/MS Herbaspirillum TOF (THAP), Structural determination plus two (Serrato et al., Lipid A seropedicae, SMR1 GC/MS Rha-deficient mutants 2012) Analysis of networks controlling Klebsiella R-TOF (DHB, the antimicrobial-peptide- (Llobet et al., Lipid A pneumoniae CMBT) dependent induction of virulence 2011) factors (Hashimoto et Mesorhizobium loti Lipid A R-TOF (DHB) Structural determination al., 2012) Outer Microcystis membrane R-TOF (DHB), Determination of monosaccharide (Fujii et al., aeruginosa NIES-87 LPS and O- GC/MS composition 2012) chain Ident. of MMAR2333 which is a Mycobacterium glycosyltransferase involved in the (Sarkar et al., LOS MALDI marinum generation of a lipid-linked 2011) caryophyllose donor. Mycobacterium R-TOF (DHB), (Rombouts et LOS Study of fatty acyl chains marinum per-Me al., 2011) Defects in LOS biosynthesis (van der Mycobacterium TOF, glycans LOS shown to alter the release of cell Woude et al., marinum (per-Me) surface proteins 2012) LOS structure shown to be Neisseria important in resistance to (Balthazar et LOS TOF (DHB) gonorrhoeae antimicrobial agents of innate host al., 2011) defence Human IgG that prevents endemic Neisseria meningococcal disease shown to (Cheng et al., LOS L-, R-TOF meningitidis recognize an internal lacto-N- 2011a) neotetraose structure Lack of lipid A pyrophosphorylation and TOF (Synapt (John et al., Neisseria sp. LOS functional lptA shown to reduce G2) 2012) inflammation by Neisseria commensals Pandoraea Structural identification of (Di Lorenzo et O-Chain TOF (DHB) pulmonicola emerging cystic fibrosis pathogen al., 2012) Plesiomonas Structural determination. Two shigelloides strain O-Chain TOF regions, one with tetrasaccharide 2012) AM36565 repeat, other with trisaccharide Outer membrane protein LptO Porphyromonas TOF/TOF (Chen et al., Lipid A found to be essential for the O- gingivalis (CMBT) 2011c) deacylation of LPS

64 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 21. (Continued)

(to mimic inflammation) produces Porphyromonas TOF (nor- (Curtis et al., Lipid A increasing proportions of gingivalis harmane) 2011) monophosphorylated, penta- acylated lipid A Free lipid A not detected in diseased dental samples. TLR2 Porphyromonas TOF (CMBT), activation attributed to LPS and (Nichols et al., Lipid A gingivalis MS/MS lipid A probably mediated by 2012) contaminating phosphorylated dihydroceramides Porphyromonas MALDI to confirm structures of (Zaric et al., gingivalis and E. LPS TOF commercial products 2011) coli Deficiency in human peptide, cathelicidin, in the cystic fibrosis Pseudomonas (Scott et al., Lipid A TOF (CMBT) lung may contribute to greater aeruginosa 2011) LPS-induced inflammation during disease phoQ Loss-of-function mutations Pseudomonas shown to contribute to high-level (Miller et al., Lipid A TOF (CMBT) aeruginosa polymyxin resistance in clinical 2011) strains PhoP-PhoQ two-component Pseudomonas regulatory system shown to (Gellatly et al., Lipid A L-TOF/TOF aeruginosa control cytotoxicity and 2012) inflammation Investigation of the inhibition of Pseudomonas (Werneburg et Lipid A MALDI LPS transport to outer membrane aeruginosa al., 2012) in peptidomimetic antibiotics Pseudomonas Vanadate and triclosan shown to (Damron et al., aeruginosa strain Lipid A TOF (CMBT) synergistically induce alginate 2011) PAO1 production Pseudoalteromonas TOF (DHB) after Structure determination and (Carillo et al., Lipid A/ LOS haloplanktis TAB 23 deacylation biological activity 2011) Characterization of galacturonosyl Rhizobium R-TOF/TOF (Brown et al., Lipid A transferase genes responsible for leguminosarum (THAP) 2012b) LPS synthesis Rhizobium Structural determination of title TOF (DHB, (Muszy ski et leguminosarum LPS compd. and of its UDP-Glc THAP) al., 2011) RBL5523 dehydrogenase mutant (exo5) Lacks 27-OH-18:0 acid in lipid A Rhizobium and is developmentally delayed leguminosarum bv. (Brown et al., Lipid A TOF (THAP) during symbiotic infection of the phaseoli (acpXL 2011b) nodulating host plant Phaseolus mutant) vulgaris Rhizobium TOF (DHB), (Kutkowska et leguminosarum bv. LPS Structure and biological activity GC/MS al., 2011) trifolii strain TA1 (Chafchaouni- Introduction of triethylamine Salmonella enterica LPS, lipid A L-TOF (DHB) Moussaoui, et citrate to hydrolyse LPS al., 2011) Evasion of human innate immunity Salmonella enterica without antagonizing TLR4 by (Matsuura et serovar Lipid A TOF mutant having penta-acylated lipid al., 2012) Typhimurium A -O-deacylation by Salmonella enterica Salmonella outer membrane serovar (Kawasaki et Lipid A R-TOF (CMBT) enzyme LpxR shown to modulate Typhimurium al., 2012b) the ability of lipid A to stimulate 14028s toll-like receptor 4 Salmonella PmrAB system is the master (Farizano et Lipid A TOF typhimurium regulator of LPS remodeling al., 2012) Shigella flexneri TOF/TOF Development of improved MALDI (Sturiale, et LPS M90T (THAP) method al., 2011b)

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TABLE 21. (Continued) Structural determination. Addition L-, R-TOF/TOF of EDTA ammonium salt to Shigella flexneri (Casabuono, et Lipid A (nor-harmane, CMBT improved the ion intensity variant X al., 2012) CMBT) for mono- and di-phosphorylated lipid A Shigella sonnei (R- Lipid A and L-TOF/TOF Structural determination by type isogenic core (DHB), GC/MS MALDI-TOF/TOF MS 2011) mutants) Identification of gene products Sinorhizobium R-TOF/TOF (Haag et al., Lipid A involved in biosynthesis of unusual meliloti (THAP) 2011) lipid A very long-chain fatty acid Streptococcus (Li et al., mutans strain EPS TOF (DHB) Structural determination 2012a) UA159 L-, R-TOF LOS and lipid Structural determination from (Silipo et al., Uruburuella suis (DHB, THAP A novel organism. Infects pigs 2012) (for lipid A) Elucidation of a novel secondary (Hankins et al., Vibrio cholerae Lipid A L-TOF/TOF hydroxy-acyltransferase and its 2011) role in innate immune recognition Bacteria shown to add glycine and (Hankins et al., Vibrio cholerae Lipid A TOF/TOF diglycine residues to lipid A to 2012) confer antibacterial resistance L-TOF, R- Structural determination. Unusual TOF/TOF phosphatidic acid substitution at (Phillips et al., Vibrio fischeri Lipid A (CMBT), ESI, the secondary acylation site of the 2011) GC/MS 3-position Structural determination. Unusual LTQ-TOF O-antigen sugars play a role in (Post, et al., Vibrio fischeri O-Chain, core (DHB), NMR colonization of the squid, 2012) Euprymna scolopes Structural determination and Xanthomonas TOF/TOF (nor- (Casabuono, et LPS involvement in plant innate axonopodis pv. citri harmane, THAP) al., 2011) immunity Yersinia Lipid A TOF (DHB) Study of acylation pattern enterocolitica 2012b) Study of molecular basis of Yersinia (Rei Lipid A TOF (DHB) temperature-dependent resistance enterocolitica 2012a) to antimicrobial peptides Yersinia TOF/TOF Development of improved MALDI (Sturiale, et LPS pestis (THAP) method al., 2011b) Production of live attenuated strain Yersinia (Sun et al., Lipid A TOF of Yersinia pestis KIM as a vaccine pestis 2011a) against plague Bacterium shown to exploit Yersinia temperature-dependent shifts in (Hajjar et al., Lipid A TOF (CMBT) pestis LPS acylation to selectively evade 2012) recognition Addition of aminoarabinose to lipid Yersinia TOF (nor- A and complete LOS core shown to (Klein et al., Lipid A pestis harmane) be important for survival of Y. pestis 2012) in macrophages For quantitative microfluidic L-TOF analysis of S- and R-type (Makszin et Various LPS (DHB/citric endotoxin components with chip al., 2012) acid) capillary electrophoresis Lipid A mono- (Faunce et al., Not stated TOF (sinapinic) Study of crystal structure phosphate 2011) aFormat (not all items present): MALDI method (matrix), other methods. prepared by chloroform/methanol and solid phase extractions defect. For further information see (Kendrick, 1963; Hughey and enriched by DEAE-Sephadex anion exchange and C18 et al., 2001). Several differences were observed between bovine solid phase extraction. The ganglioside mixtures were solubi- milk and human milk. The common gangliosides in bovine lized in methanol prior to mass spectrometry analysis. After and human milk were 2Neu5Ac-2Hex-Cer (GD3) and Neu5Ac- MALDI analysis, Kendrick mass defect analysis was performed 2Hex-Cer (GM3) but present in different amounts. Kendrick on the data sets for rapid identiﬁcation of the gangliosides. mass defect plots yielded grouping of ganglioside peaks This method scales all the measured m/z values relative to the according to their structural similarities. It was found that only m/z of CH2, which is deﬁned as exactly 14.00000 and all in human milk ganglioside was the ceramide carbon always homologous molecules will have a similar Kendrick mass even numbered.

66 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

TABLE 22. Use of MALDI MS for monitoring products of bacterial glycolipid synthesis Compounds Methodsa Notes Reference Arabinan docosasaccharide Stereoselective β-arabinofuranosylation using (Ishiwata & Ito, from mycobacterial TOF (DHB) protected arabinofuranosyl donors 2011) cell wall Arabinofuranose branched Use of aldonolactone strategy for the TOF/TOF, (Gandolfi- galactofuran tetrasaccharides introduction of the internal D-Galf, allowing glycans Donadío et al., from Mycobacterium the synthesis of oligosaccharides from the (per-Me) 2011) tuberculosis non-reducing to the reducing end. Synthesis from protected Araf thioglycoside Arabinofuranose precursor. Followed by double β- hexasaccharide from the cell (Reddy et al., TOF glycosylation with strained cyclic 2-p- wall of Mycobacterium 2012) methoxybenzyl-3,5-TIPDS Araf thioglycoside tuberculosis donor. Synthesis and inclusion complexes with some (Kwon et al., Butyryl cyclosophoraose TOF (DHB) flavonoids 2011c) Endolysins of B. anthracis bacteriophages Cell wall polysaccharides TOF/TOF recognize unique carbohydrate epitopes of (Mo et al., 2012) from Bacillus anthracis (DHB) vegetative cell wall polysaccharides Common pentasaccharide of the O-antigen of Escherichia Synthesis by a stereoselective [2+3] block (Guchhait & MALDI coli O168 and Shigella glycosylation method Misra, 2011) dysenteriae type 4 R-, L-TOF (Jeong et al., Cyclosophoraoses Rings with 19 to 23 glucose residues (DHB) 2012a) Fucosylated LOS from Bacteria glycoengineered to produce LewisY (Yavuz et al., TOF (DHB) Escherichia coli K12 epitope 2011) Inner core oligosaccharide of Chemical synthesis and immunological (Boltje et al., TOF (DHB) Francisella tularensis evaluation 2012) With ethylene glycol linking glucosamine (Lewicky et al., Lipid A mimic TOF/TOF residues 2011) Lipoteichoic acid repeating TOF (DHB Pseudopentasaccharide with two (Pedersen et al., unit from Streptococcus +ve, THAP - phosphocholine groups 2012a) pneumoniae ve) Outer core from Burkholderia Trisaccharides. Synthesised with allyl (Bedini et al., TOF (DHB) cepacia pv. Vietnamiensis aglycone 2012) Pentasaccharide repeating One-pot, two step iterative glycosylation (Panchadhayee unit of the O-antigen of MALDI followed by a series of functional group & Misra, 2011) Shigella boydii type 14 transformations Pentasaccharide repeating As its p-methoxyphenyl glycoside. (Santra & Misra, unit of O-antigen from TOF Synthesized in a convergent manner by a 2012) Escherichia coli O113 [3+2] block glycosylation strategy Pentasaccharide repeating Synthesis by sequential glycosylations (Ghosh & Misra, unit of the cell wall O-antigen MALDI with monosaccharide intermediates 2012) of Escherichia coli 19ab Tetrasaccharide repeating Synthesis using a (Sau & Misra, unit of the cell wall LPS of MALDI convergent block glycosylation strategy 2012) Escherichia coli O40 Tetrasaccharides from the O- (Santra et al., antigens of Escherichia coli MALDI Synthesis using a ‘unichemo’ approach 2012) O127 Tetrasaccharides from the O- (Santra, et al., antigens of Salmonella MALDI Synthesis using a ‘unichemo’ approach 2012) enterica O13 aFormat (not all items present): MALDI method (matrix), derivative. “MALDI” is used when the instrument is not specified. Use of infrared MALDI at 5.9 mm and with urea as the appeared superior to analyses by vacuum MALDI and was able matrix has resulted in no significant loss of sialic acid from poly- to differentiate isomers of GD1a and GD1b. sialylated gangliosides including GD1b, GT1b, and GQ1b. A method for the metabolic labeling of GSLs and Interestingly, multiple deprotonated [MnH]n ions were glycosylphosphatidylinositol with a fluorescent tag has been observed in their mass spectra, and were useful for relative devised by Pinero~ et al. (2012). Tetra-acetylated-b-N-azidoace- quantification of gangliosides in complex mixtures. Ito et al. tylglucosamine (95) was incorporated into the molecules by (2012) have coupled an atmospheric pressure-MALDI ion incubation in the intraerythrocytic stages of Plasmodium source to a quadrupole ion trap time-of-flight (QIT-TOF) mass falciparum and then linked to the fluorescent dye Click-iTTM spectrometer for acquisition of negative-ion MSn spectra and (Thermo Scientific) tetramethylrhodamine by “click” chemistry have applied it to the structural characterization of the mono- to give compounds such as 96. The tag was used for TLC sialogangliosides GM1 and GM2, the disialogangliosides GD2, detection, to quantify changes in glycosylation patterns and GD1a, and GD1b and the trisialoganglioside GT1a. The method acted as an internal matrix for MALDI analysis.

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TABLE 23. Reviews to the use of MALDI in the analysis of glycosphingolipids Subject Citations Reference Mass spectrometric analysis of neutral sphingolipids: Methods, applications, (Farwanah et al., 68 and limitations 2011) (Farwanah & Lipidomics of glycosphingolipids, structure and analysis 166 Kolter, 2012) (Flangea et al., Chip-based nanoelectrospray mass spectrometry of brain gangliosides 93 2011) Methods in comprehensive mass spectrometry-based measurement of 28 (Gassler, 2012) sphingolipids (Meisen et al., Thin-layer chromatography and mass spectrometry of glycosphingolipids 228 2011) Sphingolipid and glycosphingolipid metabolic pathways 639 (Merrill, 2011) (Sullards et al., Analysis of mammalian sphingolipids by LC/MS and tissue imaging 77 2011) (Suzuki et al., High-performance TLC/MS for analysis of neutral glycosphingolipids 41 2011a)

OAc b. Methods for sulfatides and other sulfated glycolipids O MALDI-TOF MS has been used to characterize phospholipids AcO OAc and sulfoglycolipids of pheasant sperm within a few minutes AcO NHCON3 without the necessity for previous chromatographic separation. It was noted that the matrix, 9-AA, gave better results than DHB 95, Tetra-acetylated- -N-azidoacetylglucosamine in negative-ion mode and that in positive mode it produced predominantly [MþH]þ ions, whereas DHB tended to produce a A quick method for acquiring lipid and glycolipid profiles mixture of [MþH]þ and [MþNa]þ ions (Teuber et al., 2011). from mitochondria involves the addition of the mitochondrial A method for quantifying sulfatide in serum has been suspension to the MALDI target, drying, and then applying a described (Wang et al., 2011i). Sulfatide was extracted using thin layer of 9-AA. The results compare favorably with those hexane/isopropanol and saponified to lysosulfatide with sodium from previous experiments involving TLC separations and has hydroxide. After purification, the samples were desalted by also been applied to intact membranes from the bacterium Mono-tip C18 cartridges (GL Sciences) followed by the addition Paracoccus denitrificans (Angelini et al., 2012b). of N-acetyl lysosulfatide containing d18:0-sphinganine (97)

O OHOH O OH O HO O O HO OH O O O OH OH P O O O HO O HO OH O O HO NH O O

N N NH O N

COOH

H3C CH3 N ON

CH3 CH3

68 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & as the internal standard. The compounds were analyzed by A method for lipid fingerprinting of Bacillus spp. using MALDI-TOF MS in negative-ion mode. online MALDI-TOF mass spectrometry has been described by Shu et al. (2012). Fingerprinting of bacteria is a rapidly growing NH2 area where MALDI is making a major impact but the peaks in HO the spectra constituting the fingerprint are usually not identified. Most are assumed to be peptides. However, in this work, the OH lipids, phosphatidylethanolamine (98), phosphatidylglycerol (99), and diglycosyldiacylglycerol have been used. The lipids 97, Sphinganine from the bacterial pellets were extracted with chloroform/ methanol by ultrasonication at room temperature and solids c. Studies on the glycan moiety following removal of the were removed by centrifugation. An 0.5 mL aliquot of the ceramide extract was added to 4.5 mL of the matrix solution (2,4-DHB, 2,5-DHB, THAP, SA, HABA, or CHCA were investigated) A new method for releasing free reducing glycans from GSLs and the mixture was pneumatically nebulized into suspended involves a brief treatment with ozone followed by heating in droplets. These droplets were sprayed with an aerodynamic lens aqueous buffer at 658C for 16 hr. The procedure appeared to be assembly tilted at 408 from the horizontal plane onto a tungsten highly efficient with no evidence of peeling reactions and target plate which also served as an ion repeller for the home- the released glycans could be permethylated or tagged with built reflectron mass spectrometer. A 10 Hz pulsed 266 nm laser a fluorescent label for application of traditional analytical was used to desorb and ionize the sample with an incident angle methods (Song et al., 2012a). of 508. 2,4-DHB was selected as the most appropriate matrix Fujitani et al. (2011) have developed a method for the and unique spectra were obtained for each bacterial species, elucidation of cellular GSL-glycomes based on enzymatic allowing them to be differentiated. glycan cleavage with a mixture of endoglycosylceramidase I O and II, endoglycosylceramidases derived from Rhodococcus sp., O together with glycoblotting-assisted sample preparation using a R OPO O R filterplate (MultiScreen Solvinert 0.45 mm Low Binding Hydro- 1 2 philic PTFE, Millipore, Bedford, MA) containing BlotGlyco OH O R2 beads. The glycoblotting technique enabled the quantitative 5 detection of GSL-glycans using as few as 2 10 cells. Analysis O was done by MALDI-TOF/TOF mass spectrometry and/or linkage-specific glycosidase digestion. Thirty-seven different 98, R1 = H2N-CH2-CH2-, R2 = alkyl, phosphatidylethanolamine 99 kinds of cellular GSL glycans were successfully observed in , R1 = HO-CH2-(OH)CH2-CH2-, R2 = alkyl, phosphatidylglycerol Chinese hamster ovary cells as well as murine and human Bure et al. (2011) have developed a method for the embryonic carcinoma cells. structural characterization of glycosyl-inositol-phospho-ceram- A microscale method has been developed for structural ides (GIPCs, 100), the main sphingolipids of plant tissues. analysis of glycosphingolipids and applied to analysis of these Leaves were ground in cold 0.1 N acetic acid, filtered, and compounds from the human parasitic helminth Schistosoma hydrolyzed with 0.1 N ethanolic HCl at 708C for 20 min. The mansoni cercariae. Ceramide N-deacylase was used to split the mixture was left at 208C overnight, centrifuged, and the compound in a two-phase liquid system and the resulting lyso- resulting pellet containing the GIPCs was washed with acetone glycosphingolipids were recovered from the aqueous phase, and diethyl ether. MALDI-TOF analysis in negative-ion mode cleaned with C18 NuTips, and analyzed by MALDI-TOF MS gave a quick overview of GIPC distribution. Fatty acid chains from DHB. The released fatty acids were isolated from organic and long-chain bases were analyzed by GC/MS after methyl- and aqueous phases and identified as methyl ester derivatives by amine treatment to remove any fatty acids from other com- GC/MS. The results showed clear differences in the ceramide pounds such as phospholipids. Clear differences were observed compositions of ceramide monohexoside versus ceramide penta- for the two plants studied: Six GIPC series (120 lipids) bearing hexoside species carrying a LewisX carbohydrate epitope (1/66) from two to seven glycan units were detected in tobacco BY-2 (Frank, Geyer, & Geyer, 2011). The same authors have also used cell extracts, whereas GIPCs extracted from Arabidipsis thali- endoglycoceramidase II to release glycans from adult Schisto- ana cell cultures and leaves contained only two glycan units soma mansoni worms and to show that they are different from (about 50 lipids). those in cercariae (Frank, van Die, & Geyer, 2012). Other applications of MALDI in the analysis of glycosphin- XVIII. Glycosides golipids are listed in Table 24 and papers on synthesis are in Table 25. This section covers predominantly glycosides from plants. For much of the analytical work on glycosides, MALDI appears to occupy a relatively minor position with FAB and, particularly C. Other Glycolipids ESI being the preferred techniques. Other techniques such as MALDI has also assisted in the structural elucidation of several NMR, UV, and IR spectrometry feature prominently. These other lipid types such as glycoglycerolipids, phosphatidylinosi- compounds frequently contain large hydrophobic groups requir- tol mannosides, rhamnolipids, and phenolic glycolipids (1/77) ing specific matrices for satisfactory analysis. Several investi- from a variety of sources. Much of this work is summarized in gators have addressed this problem with different conclusions Table 26. Two applications are highlighted below. depending on the target glycoside.

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TABLE 24. Use of MALDI MS for examination of glycosphingolipids Species Organ Type Methodsa Notes Reference Q-TOF Arabidopsis (DHA), ESI- Structural determination Leaves GIPC thaliana MS/MS, (see text) 2011) GC/MS Characterization of Arisaema Glucosyl R-TOF- glucocerebrosides and the (Rozema et al., Rhizomes amurense ceramide SALDI (TiO2) active metabolite 4,8- 2012) sphingadienine R-TOF Artemia Identification of novel (CHCA), (Kojima et al., franciscana Cysts GSL structures - New core - GLC, GC/MS, 2011) (brine shrimp) nonarthro series (see text) NMR TOF/TOF Sialylated gangliosides. Danio rerio (DHB), d18:1 with 16:0 and 24:1 (Vanbeselaere, ZFL cells GSL (Zebrafish) glycans (per- acids. As model for et al., 2012) Me), GC/MS human disease. L-, R- Identification of Dog and (Arteaga et al., Erythrocytes GSL (GM3) TOF/TOF compounds with 24:1 in horse 2011) (CHCA) the ceramide Changes in brain (Valdes- MALDI-QIT- Human Brain GSL gangliosides found in Gonzalez, et TOF (DHB) al., 2011b) Epitope in sperm maturation related Red blood glycoprotein to which (Katagiri et al., Human GSL MALDI-QIT cells antibody MC121 binds 2011) shown to be present in neolacto-series GSLs Brain micro and macro- TLC-IR- Study of shiga toxin (from (Betz et al., Human vascular GSL MALDI-TOF E. coli) with lipid raft 2011) endothelial (glycerol) microdomains cells Kidney transplantation shown to recover the (Wang, et al., Human Serum GSL TOF (-ve) reduced level of serum 2011i) sulfatide in end-stage renal disease patients GSL composition of stem cells shown to change Embryonic TOF/TOF, (Liang et al., Human GSL during differentiation to stem cells (per-Me) 2011c) ectodermal or endodermal lineages Hydroxylated and non- hydroxylates sulfatides Cerebral TOF/TOF, Q- (Yuki et al., Human GSL shown to be distinctly cortex Trap (9-AA) 2011) distributed in grey and white matter R-TOF Disialo-ganglioside G Breast cancer D2 (Cazet et al., Human GSL (DHB), (per- shown to be involved in cell line 2012) Me) cell proliferation Accumulation of unusual R-TOF/TOF Breast cancer gangliosides GQ3 and (Steenackers et Human Gangliosides (DHB), GSLs cell line GP3 in cells expressing al., 2012b) (per-Me) the GD3 synthase A single point mutation in the gene encoding TOF/TOF Gb3/CD77 synthase Blood (Suchanowska Human GSL (nor-harmane), found to cause a rare erythrocytes et al., 2012) ESI inherited polyagglutination syndrome

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TABLE 24. (Continued) Ceramide glycosylation TOF/TOF by glucosylceramide MCF-7 breast (Gupta et al., Human GSL (THAP), (per- synthase shown to cancer cells 2012) Me) maintains the properties of breast cancer stem cells Endoglyco- Glycosphingolipids Umbilical cord GSL (globo- ceramidase, R- SSEA-3 and -4 probably (Suila et al., Human blood series) TOF/TOF, not biomarkers for stem 2011) glycans cells Embryonic Study of changes in GSLs (Liao & Yu, Human GSL MALDI stem cells with differentiation 2012) Method for rapid detection of GM1 ganglioside in (Satoh, et al., Dog CSF GM1 TOF (DHB) CSF of dogs with GM1 2011) gangliosidosis Selective extraction of Brain and GalSph, R-TOF/TOF (Li, et al., Monkey GalSph, GlcSPh with spleen GlcSPh (DHB) 2011f) acetone Shorter fatty acyl chains Fibroblast observed for Cer and Glc- (Nagai et al., Mouse GSL TOF (DHB) Mop 8 cells Cer under heat stress 2011) conditions Lyso-GM2 accumulates (Kodama et Mouse Brain Lyso-GM2 TOF (DHB) in brains of Sandhoff al., 2011) mice. Possible biomarker Demonstration that hepatic cerebroside Serum and sulfotransferase is (Kimura et al., Mouse Sulfatides TOF liver induced by peroxisome 2012b) proliferator-activated receptor Myelin can still be formed GSL, glucosyl (Meixner et Mouse Brain TOF in the absence of UDP- ceramide al., 2011) galactose Phasianus Use to determine the R-TOF (DHB, (Teuber, et al., colchicus Spermatozoa GSL phospholipid/glycolipids 9-AA) 2011) (Pheasant) composition. Characterization of Pinellia Glucosyl R-TOF- glucocerebrosides and the (Rozema, et Rhizomes ternata ceramide SALDI (TiO2) active metabolite 4,8- al., 2012) sphingadienine Brain Imaging to study (Colsch et al., Rat GSL MALDI (hippocampus) ganglioside distribution 2011) Evaluation of

sphingolipid metabolism TOF/TOF with (Liu et al., Rat Renal cortex GSL (DHB) streptozotocin-induced 2011b) diabetes and the effects of rapamycin Dengue virus type 2 Monkey shown to recognize the Rhesus kidney LLC- carbohydrate moiety of (Wichit et al., monkey and MK2 cells, GSL TOF neutral GSLs in 2011) mosquito Mosquito AP- mammalian and mosquito 61 cells cells C18 sphingosine, C18, TOF (DHB), C20 phytosphingosine. ESI, glycans Schistosoma LewisX, Gal( 1- (Frank, et al., Adult worm GSL (per-Me) after mansoni 2012) rEGCase II 4)[Fuc( 1-3)]-GlcNAc, LacdiNAc. Different from release cercariae Q-TOF (DHA), ESI- Structural determination Tobacco BY-2 cells GIPC MS/MS, (see text) 2011) GC/MS Trypanosoma Relevance of sulphate (Acosta et al., Epimastigotes Sulfatide R-TOF (DHB) cruzi moieties 2012) aFormat (not all items present): Glycan cleavage, MALDI method (matrix), compounds studied (derivative) other methods.

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TABLE 25. Use of MALDI MS for monitoring products of glycosphingolipid synthesis Compounds Methodsa Notes Reference Compounds shown to selectively manipulate Q-TOF (Kamani et al., Adamantyl GlcCer normal cellular GSL metabolism and reduce (DHB) 2011) GSL accumulation in cells from LSD patients. Adamantyl globotriaosyl Lipid moiety of Gb3 analogues shown to (Saito et al., TOF ceramide mimics determine the trafficking of verotoxins 2012a) Bodipy-Fl-labeled TOF (Sarver et al., Synthesis and electrophoretic separation glycosphingolipids (CHCA) 2012) (Sugiura et al., Chondroitin sulfate library TOF Use of sulfotransferases 2012) -D-GalNAcp(1 4)[ -D- Synthesis of unique GSL from Aplysinella (Fujita et al., TOF, FAB Fucp(1 3)]- -D- rhax 2011c) GlcNAcp(1 )Cer Large-scale production by lung squamous-cell (Shimura et al., Ganglioside analogues TOF carcinoma RERF-LC-AI cells cultured in 2012b) HyperFlask Gangliosides with Neu5Ac- TOF (Nohara et al., 2 3Gal and Neu5Ac- As ligand for influenza A viruses (CHCA) 2012) 2 6Gal Reaction by reductive amination for binding GM1 plus aminophenyl TOF to gold electrodes to study Vibrio cholera (Seo et al., 2012) disulfide toxin interaction GSLs from Schistosoma Stereo-controlled syntheses of three neutral (Kanaya et al., TOF mansoni GSLs and six oligosaccharide derivatives 2012) Heparan sulfate glycopeptide: (Yang et al., MALDI Chemical synthesis Syndecan-1 2012a) Synthesis and investigation of the positional Linker-attached Lc and 4 MALDI effect of acyl and bulky silyl groups on D- (Hsu et al., 2012) IV2Fuc-Lc 4 glucose-based thiotoluenyl donors Use of ManNAc analogues to engineer GM3 (Whitman et al., Modified GM3 gangliosides TOF with modified sialic acids in cell culture 2011) Neurostatin and gangliosides (Romero- R-TOF/TOF O-acetylated in the outer Synthesis using a sialate transferase (DHB) sialic acids 2012) Tetramethylrhodamine- Fluorescent derivative labelled on the amino (Tanaka et al., labelled Gal-(1,4)-S- Gal- TOF group of the ceramide 2012) ceramide Thiogalactopyranoside- Thiogalactopyranosides shown to be resistant (Adlercreutz et TOF (DHB) ceramide to hydrolysis by -galactosidases al., 2012) aFormat (not all items present): MALDI method (matrix) “MALDI” is used when the instrument is not speciﬁed.

Of ﬁve matrices (DHB, CHCA, THAP, DHAP, and s-DHB) estimate the degree of polymerization accurately. CHCAyielded only s-DHB, at a concentration of 20 mg/mL in 70% aqueous acceptable spectra for dimers but was much less satisfactory acetonitrile enabled Stringano et al. (2011) to detect the larger than s-DHB for the tetramers and did not detect the pentamers. proanthocyanidins (such as the dimer 101 and glycosylated However, not all the concentrations of s-DHB were suitable for analogues) from Onobrychis viciifolia (sainfoin). Compounds the detection of Na adduct ions. Thus, at a concentration of up to a DP of 12 were observed but although signals could also 5 mg/mL in 30% aqueous acetonitrile, trimeric proanthocyani- be seen at higher m/z values, the resolution was insufﬁcient to dins but not larger oligomers were detected. However, the

OH CO OH

O O HO O

HO NHAc HO OH HO O OH O

HO O P O

OH O OH HO OH O

100, glycosyl-inositol-phospho-ceramide (GIPC)

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TABLE 26. Use of MALDI MS for examination of archaea, bacterial and fungal glycolipids and related compounds Species Glycolipid Instrumentsa Notes Reference Biosynthesis of cell wall Aspergillus Glycosylinositol- polysaccharide galactomannan (Engel et al., R-TOF (ATT) fumigatus phosphorylceramide shown to require intraluminal 2012) GDP-mannose Enzymatic activities of (Wörmann et Bacillus subtilis Lipoteichoic acid TOF (DHB) lipoteichoic acid synthesis al., 2011) enzymes Phospholipids, TOF (2,4-DHB, Lipid fingerprinting of Bacillus (Shu, et al., Bacillus Spp. diglycosyldiacyl- 2,5-DHB, THAP, spp. using online MALDI-TOF SA, HABA, and 2012) glycerol CHCA) mass spectrometry (see text) Two and three sophorose units Candida sp. Sophorolipids R-TOF (DHB), (Price et al., linked with 18-OH-Δ9- NRRL Y-27208 (biosurfactants ) GC/MS, NMR 2012) octadecanoate Investigation of two α(1,2)- Corynebacterium manno-pyranosyltransferases, (Mishra et al., Lipoarabinomannan L-TOF (DHB) glutamicum MptC and MptD in mannan 2011b) branching Differential arabinan capping Corynebacterium shown to modulate innate (Mishra et al., Lipoarabinomannan L-TOF (DHB) glutamicum immune responses and to impact 2012a) T helper cell differentiation Enterococcus Lipoteichoic acid CaOH inactivated LTA by (Baik et al., TOF 2 faecalis (LTA) deacylation of lipid 2011) Structural determination. Enterococcus R-TOF (DHB), Repeating unit has two residues (Bychowska et faecium strain Teichoic acid GLC, GC/MS of D-GalNAc, glycerol, and al., 2011) U0317 phosphate Structural determination. Shown MPIase TOF/TOF (Nishiyama et Escherichia coli to be essential for membrane (glycolipozyme) (DHB), FT-ICR al., 2012) protein integration Biosynthesis found to require Escherichia coli Polymannose unique combination of single- (Greenfield, et Serotypes O8 and TOF/TOF Lipopolysaccharide and multiple-active site al., 2012) O9a mannosyltransferases [→3)-α-D-GlcA- From fractions rich in stearic Helicobacter α TOF (CHCA), (Ferreira et al., (1→4)- -D-Glc- acid suggesting presence in cell- pylori NMR 2011a) (1→] repeat linked surface glycolipids to glycerol TOF (DHB), Structural determination. Lactobacillus Lipoteichoic acid TOF/TOF, Free (Jang et al., Different from other known plantarum (LTA) compds or O- 2011) structures Ac derivs. Mycobacterium Valine- or leucine- Structural identification. Avium- TOF/TOF (Ichimura & containing Variation in tripeptide portion of intracellulare (DHB) Kasama, 2012) glycopeptidolipids molecules Complex Mycobacterium Phenolic glycolipids bovis bacillus R-TOF (DHB), Lipid phenotype of two distinct (Naka et al., and phthiocerol calmette-guérin GC/MS subpopulations 2011a) dimycocerosate Tokyo 172 Mycobacterium Glycopeptidolipid TOF (DHB), (Naka et al., Structure and host recognition intracellulare (Serotype 13) GC/MS 2011b) Structural determination and (Elass- Mycobacterium Dimycolyl- toll-like receptor 2-dependent TOF (DHB) Rochard et al., marinum diarabino-glycerol proinflammatory activity of 2012) dimycolyl-diarabino-glycerol Mutant defective for major cell Mycobacterium wall-associated lipids is highly Phthioglycol (Alibaud et al., marinum TesA TOF (DHB) attenuated in Dictyostelium diphthioceranates 2011) mutant discoideum and zebrafish embryos Discovery of novel hsp65 Mycobacterium Glycopeptidolipids (Kim et al., TOF genotype associated with the massiliense (GPLs) 2012a) rough colony morphology

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TABLE 26. (Continued) Deciphering the role of CD1e Phosphatidyl-myo- (Cala-De Mycobacterium R-TOF/TOF protein PIM processing for inositol mannosides Paepe et al., smegmatis (HABA) presentation by CD1b to T (PIMs) 2012) lymphocytes Investigation of the biosynthetic Mycobacterium Glycopeptidolipids (Vats et al., TOF pathway and structure of the acyl smegmatis (GPLs) 2012) chain of GPLs Lipoglycans shown to contribute Mycobacterium TOF, -ve (Krishna et al., Lipoglycans to innate immune detection of smegmatis (DHB) 2011) mycobacteria Disruption of enzyme causing arabinosylation of (Larrouy- Mycobacterium PIMs TOF arabinogalactan and Maumus et al., smegmatis lipoarabinomannan had no effect 2012) on PIMs Mycobacterium Glycopeptidolipids TOF/TOF Structural determination and (Fujiwara et smegmatis J15cs (GPLs) (DHB) macrophage activation al., 2012) strain TOF/TOF Mycobacterium Identification of new acylated (Layre et al., Sulfoglycolipids (HABA, DHB), tuberculosis forms 2011) NMR Structure different from that in Mycobacterium L-TOF (DHB), (Torrelles et Lipomannans Mycobacterium smegmatis (non- tuberculosis GC/MS al., 2011) pathgenic) Exposure of Mycobacteria to Mycobacterium cell wall-inhibitory drugs shown (Rombouts et Arabinoglycerolipid TOF (DHB) tuberculosis to decrease production of al., 2012) arabinoglycerolipid Mycobacterium Phenolphthiocerol Influence of envelope lipids on (Krishnan et R-TOF/TOF tuberculosis dimycocerosate virulence al., 2011) Divergent effects of mycobacterial cell wall Mycobacterium glycolipids (Mazurek et tuberculosis and Lipoarabinomannans TOF on maturation and function of al., 2012) M. bovis human monocyte- derived dendritic cells Natronococcus TOF (9-AA) (Angelini et occultus and N. Glycocardiolipins Structural determination from TLC plate al., 2012a) amylolyticus Insecticidal activity Pseudomonas sp. (Kim et al., Rhamnolipid TOF against green peach aphid EP-3 2011c) (Myzus persicae) Mannosylribitol lipid Pseudozyma TOF (CHCA), and Structural determination. (Morita et al., parantarctica GC/MS, NMR, mannosylarabitol Biosurfactants 2012) JCM 11752 HPLC lipid Chemical composition, Scomber Glycolipid antiproliferative and antioxidant (Bae & Lim, japonicus (chub TOF (CHCA) (unspecified) properties of lipid classes in 2012) mackerel) ordinary and dark muscles Staphylococcus Interaction of type A lantibiotics simulans 22 and Teichoic acids L-TOF (ATT) with undecaprenol-bound cell Micrococcus 2012a) envelope precursors luteus DSM 1790 Production of sophorolipid Starmerella TOF (CHCA), glycolipid biosurfactants from (Takahashi et bombicola NBRC Sophorolipids GC/MS sugarcane molasses with the al., 2011b) 10243 (yeast) yeast Streptomyces Structure and (Cot et al., Lipoteichoic acid TOF (DHB) hygroscopicus immunomodulatory activities 2011) Galp( 1-6)Glcp-N- acyl( 1-2)Glc Thermus TOF (DHB), p( 1-)acyl Gro and Structural determination. Acyl (Suda et al., thermophilus 2 ESI-TOF, (Per- Galf( 1-2)Galp( 1- groups = iso-15:0 and iso-17:0 2012) HB8 Me) 6)GlcpN-acyl( 1-2)- Glcp( 1-)acyl2Gro Structural determination. Trichomonas L-TOF (DHB), Polyrhamnose backbone with (Ryan et al., Surface lipoglycan vaginalis GC/MS, ESI branches of Xyl and poly- 2011) LacNAc aFormat (not all items present): MALDI method (matrix), compounds run (derivative), other methods.

74 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & detection of trimeric proanthocyanidins was not possible when sides of anthocyanins were found to be easily monitored the same matrix was used at concentrations of 20 mg/mL in 70% molecular markers of the hybrid varieties. Three matrices, DHB, aqueous acetonitrile. The best s-DHB matrix concentration for sinapinic acid and CHCA were compared and sinapinic acid was detecting larger proanthocyanidins was found to be 20 mg/mLin found to give the best results. PSD was found to be useful for 70% aqueous acetonitrile. differentiating isobaric 3,5-O-diglucosides from the hybrid ESI and MALDI-TOF have been compared for the analysis cultivars from acylated 3-O-glucoside anthocyanins (Picariello of five polyacylated anthocyanins such as 102 that contain more et al., 2012). than two esterified aromatic acid molecules in the side chains. A MALDI-TOF MS-based method using only small ESI was found to be advantageous for the detection of individual amounts of material has been developed for rapid differentiation molecular ions, whereas MALDI was more useful for the between Panax ginseng and P. quinquefolius, two herbal detection of characteristic fragment ions originating from the medicines with similar chemical and physical properties but anthocyanidin. Although DHB was an effective matrix for different therapeutic effects. Analysis by MALDI was per- the intact molecules, CHCA was preferred for the aglycones. In formed either after a brief extraction step or directly from small particular, for studies of polyacylated anthocyanins with two pieces of raw samples. Different patterns of ginsenosides and acylated glycoside chains, fragment ions originating from small chemical molecules were found between the two types of anthocyanidin could only be observed by MALDI-TOF with ginseng. The method was also used to differentiate red ginseng CHCA as the matrix (Kasai, Saito, & Honda, 2011). or P. quinquefolius adulterated with P. ginseng from pure P. ginseng and pure P. quinquefolium (Lai et al., 2012). OH An ionic liquid-based microwave-assisted extraction (ILMAE) method, claimed to be more effective and environ- HO O OH ment friendly than conventional methods, has been developed O for the extraction and quantification of flavonoid glycosides in OH pigeon pea leaves. Nine different types of ionic liquids with OH different cations and anions were investigated. The results indicated that variations in the anion and cation composition had OOH significant effects on the extraction of the glycosides with 1.0 M 1-butyl-3-methylimidazolium bromide as solvent (Wei et al., 2012b). OH Other applications of MALDI to the analysis of glycosides HO and other natural products are summarized in Table 27 and OH papers describing synthesis of glycosides are listed in Table 28.

101, Proanthocyanidin dimer XIX. MEDICAL APPLICATIONS MALDI-TOF MS has been used to profile the anthocyanins from the berry skins of 23 red grape varieties to develop a Research in this area mainly involves the search for biomarkers method to differentiate authentic Vitis vinifera from hybrid and in finding the cause(s) of disease. Much of the work targets cultivars. Anthocyanins were profiled and acyl-3,5-O-digluco- N-linked glycans with transferrin a favorite reporter

HO O OH

O O HO O HO OH O OH OH O OH HOHO O O HO OH HOHO O OH O OH O O OH HO OH O OH O OH

O OH

102

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TABLE 27. Use of MALDI mass spectrometry for the study of natural products Species Compound Instrumenta Notes Reference Glycosides Structural determination of Oleanane glycosides TOF, ESI, (Hamed et al., Alhagi maurorum 3 new compounds. (from roots) NMR 2012) Antiproliferative activity

2011b) Allium Structural determination. TOF, GC/MS, ampeloprasum var. Steroidal saponins haemolytic effects and NMR, IR 2011a) porrum antiinflammatory activity 2012) Allium Anthocyanin-flavonol TOF (CHCA), (Saito et al., Structural determination. complexes PSD 2012b) Identification of two new Oleanane-type TOF, ESI, (Nhiem et al., Aralia elata and four known compds. triterpene saponins NMR 2011) Antiinflammatory Investigation of processing Aronia, sp (Howard et al., Cyanidin glycosides R-TOF (DHB) and storage on berry (chokeberries) 2012) polyphenols Asterias amurensis Asterosaponins R-TOF/TOF Isolation of three new and (Hwang et al., (starfish) (steroid glycosides) (DHB), FAB four known saponins 2011) Astragalus aureus Cycloartane-type TOF (CHCA), Ident. of eight new and ten al., triterpene glycosides ESI, GLC known structures 2011) Cycloartane TOF (CHCA), (Savran et al., Astragalus erinaceus Structural identification glycosides NMR, ESI 2012) Cycloartane- and TOF (CHCA), Astragalus hareftae (Horo et al., oleanane-type ESI, NMR, Structural determination (NAB.) SIRJ 2012) triterpenoids ORD Astragalus Cycloartane-type TOF (CHCA), Ident. of six new and six stereocalyx Bornm. triterpene glycosides ESI, GLC known glycosides 2012) TOF (DHB), Blepharis edulis Structural determination and Phenylethanoids NMR, UV, (Ashour, 2012) (Forssk.) Pers. antioxidant activity HPLC Triterpene hexahydroxy- TOF (DHB) Structural determination (Huang et al., Castanopsis fissa diphenoyl esters and FAB, NMR, from leaves. Moderate 2011d) quinic acid purpuro- UV, LC, TLC lipase inhibition activity gallin carbonyl ester Castanopsis Phenolic glucosides TOF, FAB, Structural determination (Huang et al., sclerophylla and an ellagitannin NMR from leaves 2012c) TOF Identification of two new (sinapinic), (Rubio-Moraga Crocus sativus Triterpenoid saponins oleanane-type saponins, ESI-MS/MS, et al., 2011) named Azafrine 1 and 2 NMR R-TOF/TOF, Crocins and Comparison of tandem (Koulakiotis, et Crocus sativus L. Q-TOF picrocrocin MS/MS techniques al., 2012) (THAP), ESI TOF (CHCA), Identification of glycolipids Cryptpcoccus (Morita et al., Cellobiose lipids TLC, HPLC, biosurfactants and humicola JMC 1461 2011a) NMR interfacial properties Cryptpcoccus (Imura et al., Cellobiose lipids TOF (CHCA) Study of gellation properties humicola 2012) R-TOF Cyclamen Ident. of five new and four (Altunkeyik et Triterpene glycosides (CHCA), ESI, hederifolium known glycosides al., 2012) GLC TOF (CHCA), Structural derermination. (Perrone et al., Digitalis ciliata Steroidal glycosides ESI, MS/MS, Two new and eight known 2012) NMR compounds Diospyros kaki Isolation and tyrosinase (Xue et al., Anthocyanins TOF (CHCA) (persimmon) inhibitory effects 2011b) Erigeron canadensis Polyphenolic- Anticoagulant and anti- (Pawlaczyk et TOF L. polysaccharide platelet activity al., 2011) Mono- and di-galloyl L-TOF (DHB), Extraction and identification (Vázquez et al., Eucalyptus globulus glucose, quercetin-3- ESI, HPLC, of antioxidants 2012) O-rhamnoside GPC

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TABLE 27. (Continued) 3β-O-Glycosylated OH Group at C-18. Eupentacta 16β-acetoxy-9β-H- intermediate in 4,4,14- (Silchenko et al., fraudatrix (sea TOF (CHCA) lanosta-7,24-diene- trimethylsterol glycoside 2012) cucumber) 3b,18,20β-triol biosynthetic pathway Gymnema sylvestre (Zhang et al., Triterpenoid saponin TOF, ESI Structural determination (vine) 2012c) TOF (CHCA), Structural determination of Helleborus (Muzashvili et Furostanol glycosides ESI, NMR, nine compds, caucasicosides caucasicus al., 2011) ORD E–M Imaging to locate compds. R-TOF/TOF Investigation as chemical (Van Dyck et al., Holothuria forskali Triterpene glycosides (CHCA/ defense compds. against 2011) aniline) predatory fish Resin glycosides Structural determination. TOF, ESI, (Cruz-Morales et Ipomoea alba (albinosides I−III) Potentiates vinblastine GC/MS, NMR al., 2012) from seeds effect. (Castañeda- Resin glycosides Ipomoea purga Isolation and identification Gómez & (purginosides I and II MALDI (jalap - herbal drug) (complex glycolipids) Pereda-Miranda, and purging I) 2011) 1,2,4,6- and 1,2,3,4,6- TOF, FAB, Structural identification. Juglans sigillata (Si et al., 2011) O-galloyl-β-D-Glc NMR Antioxidant activity Myrica rubra Sieb. R-TOF (Xu, et al., Anthocyanins Structural determination et Zucc, (waxberry) (CHCA) 2011c) Flavonol glucoside (Pereira do Paepalanthus TOF (CHCA), Structural identification and cyclodimer and other Amaral et al., geniculatus LC/MS, GLC antioxidant properties compounds 2012) (Stefanowicz- Cytotoxic activity against Paris quadrifolia Steroid saponins TOF (DHB) Hajduk et al., human tumor cells 2011) Phaeodactylum Sulfoquinovosyl- QIT-TOF From three strains. MSn. (Naumann et al., tricornutum diacyglycerides (DHB), TLC Position of fatty acids 2011) Phytoceramides and TOF, LC/MS, Pterospermum Identification of four new (Dixit et al., acylated phytosterol NMR, ORD, acerifolium (Willd) and five known compounds 2012) glucosides IR Raspailia agminata Agminosides Identification of five TOF, ORD, (Wojnar & (New Zealand (acetylated compounds with up to five NMR, GLC Northcote, 2011) marine sponge) glycolipids) Glc residues Rehmannia Structural identification of TOF, glutinosa Libosch. Carotenoid glycoside neo-rehmannioside and (Fu et al., 2011a) LC(ESI)-MS (di-huang) five known compounds (Novikov et al., Rosa spinossima L. Anthocyanins TOF/TOF Phytochemical study 2011) Rubus loganobaccus Ident. and quantification of and Rubus R-TOF short oligomeric (Furuuchi et al., Proanthocyanidins baileyanus cross (DHB), HPLC proanthocyanidins and other 2011) (boysenberry) polyphenols Ruscus aculeatus Ident of 17 compounds (Mari et al., Steroidal glycosides TOF (CHCA) (Liliaceae) including 6 new 2012) Identification of 11 new TOF (CHCA), (Napolitano et Ruscus ponticus Steroidal glycosides compounds from ESI, NMR al., 2011) underground plant parts TOF (CHCA), Structural determination of ESI, HPLC, (Hamed et al., Salsola imbricata Triterpene saponins two new and three known NMR, GLC, 2011) compounds from roots TLC (de Paula TOF, GC/MS, Structural determination and Samanea saman Triterpene saponin Barbosa et al., TLC haemolytic activity 2012) Iridoid, TOF, ESI, Structural determination, (Kirmizibekmez Sideritis trojana phenylethanoid and TLC, NMR, antioxidant properties et al., 2012) flavonoid glycosides OR Solanum tuberosum Thermal degradation and R-TOF/TOF (Nayak et al., (potato 'Purple Anthocyanins impact on antioxidant (CHCA) 2011) Majesty') capacity

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TABLE 27. (Continued) Staurocucumis Structure determination. liouvillei(Vaney) TOF, ESI, Rare 3-O-methylquinovose (Antonov et al., Triterpene glycosides (Antarctic sea NMR as terminal monosaccharide 2011) cucumber) residue Study of MS/MS spectra TOF/TOF (Prinsep & Tolypothrix nodosa Tolyporphins and identification of two (CHCA), Lift Puddick, 2011) new compounds. Development of new Vaccinium TOF, FT-ICR standard for 4-(dimethyl- (Feliciano et al., macrocarpon Ait. Proanthocyanidins (DHB) amino)cinnamaldehyde 2012) (cranberry) assay Method for differentiating Vitis vinifera L. (red R-TOF (Picariello, et al., Anthocyanins from hybrid grapes (see grape) (sinapinic) 2012) text) Ident. of three spirostane, TOF (CHCA), one furostane and one Steroidal saponins (Skhirtladze et Yucca gloriosa L. LC/MS, NMR, cholestane glycosides, along (from rhizomes) al., 2011) ORD, HPLC with seven known compounds Glycoproteins, glycopeptides and amino acids R-TOF Hydroxyproline rich Structural characterization Datura stramonium (CHCA), PSD, (Mandal, 2012) glycopeptide and antifungal activity glycopeptide Dendroaspis TOF/TOF From venom. Hex-HexNAc (Quinton et al., angusticeps (green Glycopeptides (DHB), ETD, at Ser-15 2011) mamba) Branched sugar chain with (Kang et al., Gum ghatti Glycoprotein TOF (DHB) attached peptides 2012a) TOF/TOF Glycosylated Structural determination of Nostoc commune (DHB), (Matsui et al., mycosporine-like two compounds with radical (cyanobacterium) LC/MS, UV, 2011) amino acids scavenging activity NMR L-TOF

(intact), R- Determination of variability Solanum tuberosum (Bárta et al., Patatin (glycoprotein) TOF (tryptic in glycan concentration with L. (potato) 2012) peptides) variety (DHB) Structural identification of Vipera ammodytes ammodytagin, (Kurtović et al., Glycoprotein L-TOF ammodytes (heterodimeric metallo- 2011) proteinase from venom) Other compounds Arctium lappa Lignans and QIT-TOF Comparative analysis in (Liu et al., (burdock) caffeoylquinic acid (DHB) roots and seeds 2012c) TOF (9- Structural determination by Pyrococcus furiosus Archaeol and (Lobasso et al., aminoacridine) coupled TLC-MALDI-TOF (archaeon) caldarchaeol lipids 2012) PSD, TLC MS Evaluation of the effects of tannins on the extent and (Pellikaan et al., Various plants Tannins TOF (s-DHB) rate of in vitro gas and CH4 2011) production aFormat (not all items present): MALDI method (matrix), other methods. glycoprotein for disease monitoring. Caslavska et al. (2012) cell line derived from human umbilical vein endothelial cells have developed anti-transferrin spin columns containing poly- using both MALDI and ESI techniques together with exo-and clonal rabbit anti-human transferrin antibodies linked to Sephar- endo-glycosidase digestions. The polylactosaminoglycan chains ose 4 Fast Flow beads for the efficient extraction and were found to be less sialylated and fucosylated than normal but determination of carbohydrate-deficient transferrin in serum. to contain more extended and branched chains than those of The method enabled carbohydrate-deficient transferrin to be human umbilical vein endothelial cells. Furthermore, the poly- determined in all samples investigated. lactosaminoglycan chains were shown to be not restricted to a Wang, Wu, and Khoo (2011) have noted that many MS- specific antenna including the biologically important 6-antenna. based glycomic and glycoproteomic methods in this area report changes in terminal sialylation and fucosylation at specific A. Cancer positions of the terminal N-acetyllactosamine units rather than details of the linear or branched poly-N-acetyllactosamine Lin et al. (2011e) have developed a method to elucidate the extensions from the trimannosyl-chitobiose core of N-glycans. structures of N-glycans from serum glycoproteins and to utilize They have addressed this omission with the use of an EA.hy926 fucosylated glycans as potential markers for pancreatic cancer.

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TABLE 28. Use of MALDI MS for monitoring products of the synthesis of glycosides Compounds Methodsa Notes Reference Synthesis using dextransucrase from (Woo et al., Ampelopsin glucosides TOF (DHB) Leuconostoc mesenteroides B- 2012) 1299CB4 Glucosylation by Leuconostoc Astragalin (kaempferol-3-O-β-D- (Kim et al., L-TOF (DHB) mesenteroides B-512FMCM glucopyranoside 2012e) dextransucrase Synthesis by gold(I)-catalyzed (Ma et al., Digitoxin MALDI glycosidation of glycosyl o- 2011b) alkynylbenzoates Synthesis and apoptosis-inducing (Wang et al., Diosgenyl saponin analogues MALDI activity on A549 human lung 2012a) adenocarcinoma Use of UGT78D1 (Ren et al., Flavonol 3-O-glycoside FT-MS glycosyltransferase 2012a) Synthesis via gold(I)-catalyzed (Li et al., Lupane-type saponins MALDI glycosylation with glycosyl o- 2011g) alkynylbenzoates as donors Enzymatic synthesis of glycolipid Mannosylerythritol lipid-D from (Fukuoka et TOF (CHCA) biosurfactant, and its aqueous phase Pseudozyma and Ustilago fungi al., 2011) behavior TOF/TOF (DHB, THAP, Transglycosylation with Acremonium (Mazzaferro et 4-Methylumbelliferyl-rutinoside CHCA/Et3N, sp. α-rhamnosyl-β-glucosidase al., 2012) nor-harmane) Oligomeric 4-(glycosyloxy)benzoate Synthesis of clemoarmanoside A and (Li et al., macrocyclic glycosides from various MALDI clemahexapetoside A 2011i) plants used in folk medicine Use of alkali-tolerant thermostable (Weignerová Quercetin-3-β-D-glucopyranoside TOF (DHB) α-L-rhamnosidase from Aspergillus et al., 2012) terreus Solamargine ((25R)-3β-{O-α-L-Rhap- From the berries of solanum TOF (DHB), (Wei & Du, (1→2)-[O-α-L-Rhap-(1→4)]-β-D- aculeastrum. Synthesized in 26.8% ESI 2012) Glcpoxy}-22α-N-spirosol-5-ene) overall yield Steroidal saponins from Ruscus To develop HPLC-ESI/ITMS (Mari, et al., TOF (CHCA) aculeatus (Liliaceae) analytical method 2012) Steviobioside (steroid), from Stevia TOF/TOF Modified with pyridine carboxylic (Sharipova et rebaudiana (DHB) acid hydrazides. Anti-TB al., 2011) Synthesis and antimicrobial activity (Korochkina et Steviobioside glycoside TOF of derivatives containing onium al., 2011) nitrogen Synth. and antituberculosis activity TOF/TOF (Kataev et al., Steviobioside glycoside of derivatives containing hydrazone, (DHB) 2011) hydrazide, and pyridinoyl moieties Synthesis in 11 steps in 15% overall Stryphnoside A (triterpene saponin) TOF (CHCA), (Lv et al., yield from naturally abundant from Stryphnodendron fissuratum TLC, NMR 2011) oleanolic acid aFormat (not all items present): MALDI method (matrix), other methods. “MALDI” used when instrument not specified. This assay, from only 10 mL of serum, was applied to haptoglo- of a1-acid glycoprotein is also associated with cancer and bin from the serum of 16 pancreatic cancer patients and 15 inflammation. It possesses a triantennary glycan with fucose on matched (5 normals, 5 chronic pancreatitis, and 5 type II the equivalent antenna but is frequently incorrectly identified as diabetes) controls. Haptoglobin was extracted using a monoclo- a core-fucosylated glycan, particularly when “identification” is nal antibody; the glycans were released with PNGase F, only the result of matching its mass to a database. desialylated and permethylated. Analysis was done by MALDI- Drake et al. (2011) have described a mass spectrometry- QIT-TOF MS. Eight desialylated N-glycans were identified and based method that incorporates lectin affinity chromatography a bifucosylated triantennary structure was reported for the first for enrichment of proteins that carry specific glycan structures. time in pancreatic cancer samples. Both core and antennary Because increases in sialylation and fucosylation are prominent fucosylations were elevated in pancreatic cancer samples among cancer-associated modifications, Sambucus nigra agglu- compared to samples from benign conditions and the study tinin (SNA) and Aleuria aurantia lectin (AAL), lectins that bind demonstrated that a serum assay based on haptoglobin fucosyla- sialic acid- and fucose-containing glycans, respectively, were tion patterns using mass spectrometric analysis may serve as a used to extract the target glycans. Fucosylated and sialylated novel method for the diagnosis of pancreatic cancer. Tsai et al. glycopeptides from human lactoferrin and high-mannose gly- (2011) have also noted up-regulation of haptoglobin in lung cans from yeast invertase served as positive and negative cancer and have identified attached trisialylated triantennary controls, respectively. Samples were loaded onto the lectin glycans with fucose on the 4-branch of the 3-arm. Up-regulation columns, separated by HPLC into flow-through and bound

Mass Spectrometry Reviews DOI 10.1002/mas 79 & HARVEY fractions, and treated with PNGase F to release the N-linked nanostructure-initiator mass spectrometry based enzyme assay glycans. The deglycosylated peptide fractions were examined (Nimzyme), was applied to the disaccharides maltose, cellobi- by ESI HPLC-MS/MS and 122 human plasma glycoproteins ose, and lactose. These carbohydrates contained a pentanethiol containing 247 unique glycosites were identified. MALDI-TOF linker (103) and were labeled with reagents such as 104 was used to identify glycans in the two reference glycoproteins. containing different fluorinated substituents. After enzyme hydrolysis, the product was, thus, labeled with a different mass tag depending on its origin and the method was applied to the B. Congenital Disorders of Glycosylation (CDG) analysis of enzymes in crude cell lysates with product monitor- A method for N-glycan profiling from plasma glycoproteins by ing by MALDI-TOF/TOF MS. MS to detect CDG type II has been developed by Guillard et al. OH (2011a). N-glycans were released from glycoproteins by OH OH O PNGase F digestion, permethylated and measured with a O OSH MALDI linear ion trap mass spectrometer. A set of 38 glycans O HO OH was used for quantitative measurements. CDGs due to mannosyl HO OH (a-1,6-)-glycoprotein b-1,2-N-acetylglucosaminyltransferase 103 (MGAT2), b-1,4-galactosyltransferase 1 (B4GALT1), and , Tagged lactose SLC35C1 (a GDP-fucose transporter) defects were diagnosed directly from the N-glycan profile. It was concluded that MALDI-ion trap analysis of plasma N-glycans identifies fea- XXI. INDUSTRIAL APPLICATIONS tures that discriminate between primary and secondary causes of underglycosylation and should be applied as the first step in the A. Food Industry diagnosis of all patients with an unsolved CDG type II. Table 29 lists applications of MALDI analysis to this field, The use of MALDI in the study of food allergenomics has been and Table 30 lists relevant review articles. included in a review by Picariello et al. (2011) (214 references).

XX. GLYCOSYLATION AND OTHER REACTION 1. Oligosaccharides in Milk MECHANISMS Three relevant reviews have been reported: analysis and role of MALDI is used in this area mainly for the monitoring of the oligosaccharides in milk (Ruhaak & Lebrilla, 2012a) (81 products of enzyme reactions. Table 31 lists papers published references); advances in the analysis of human milk oligosac- during the review period. A few general applications have been charides (Ruhaak & Lebrilla, 2012b); and Lewis blood group reported. Thus, a MALDI-TOF-based assay for chitinase activi- epitopes in human milk liposaccharides (Blank et al., 2012a). ty has been described (Price & Naumann, 2011). The assay used A method has been described for structural analysis of high unmodified chitin oligosaccharide substrates and was readily molecular weight carbohydrates in human milk, a task that is achievable on a microliter scale. Reactions were initiated by the still described as challenging (Blank et al., 2012b). The method addition of chitinase to the chitooligosaccharides and, after combines separation by two-dimensional HPLC and analysis by incubation, reactions were stopped by adding an equal volume MALDI-TOF MS (with and without permethylation), GC/MS, of DHB matrix and immediately spotting the solution onto the and exoglycosidase digestion. As examples of the operation of MALDI target. The mass spectrum could be acquired in the method, two carbohydrates, one with a difucosylated octaose approximately 2 min, as opposed to typically 30–40 min for a core and the other with a trifucosylated decaose core, were single run with a HPLC-based assay. In addition, because the analyzed. The results showed the presence of one terminal substrate and product chitomers were visualized simultaneously LewisA and one internal LewisX epitope on the octaose which in the TOF spectrum, information on the cleavage site and was identified as a difucosylated iso-lacto-N-octaose (105). The mechanism of the enzyme activity could be obtained. The assay other compound was shown to be a trifucosylated, doubly was used to monitor the purification and transgenic expression branched lacto-N-neo-decaose (106) that was claimed to be new of plant class IV chitinases. type of human milk oligosaccharide. A method using mass tags for rapidly differentiating A method using hydroxyapatite for concentrating casein glucosidases whose common reaction products are glucose has phosphopeptides (CPP) in small amounts in milk samples (raw, been reported by Deng et al. (2012). The technique, called pasteurized, etc.) that had been heated at various temperatures

CF3 H3C CH3 (CF2)4 F N CF3 NH O HN N

O HO O

104, Fluorine-labelled reagent. The arrow shows the point of attachment of the tagged carbohydrate

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bioconjugation reactions using mutant glycosyltransferases for site-specific labeling with sugars carrying chemical handles (Ramakrishnan et al., 2011). Liu et al. (2011a) have evaluated a method for extracting drugs from pharmaceutical preparations with maintenance of quality and structural integrity, particularly of the N-glycans. Recombinant human follicle stimulating hormone (follitropin alpha for injection) from a pharmaceutical source was used as an example. The method involved extraction with a Hitrap DEAE- FF (GE Healthcare) column followed by elution with 2 mM and times has been described (Pinto et al., 2012). Un-phosphory- phosphate plus 500 mM NaCl. The eluted compound was lated peptides that were not retained by the hydroxyapatite were collected and spun for 1 hr at 3000 rpm at 48C and was then removed by washing with three buffers and the phosphopeptides washed with 5 mM phosphate containing 150 mM NaCl pH 7.4 were eluted with water for analysis by MALDI-TOF MS. The and stored at 808C. N-glycans were analyzed by MALDI-TOF lactosylated phosphopeptides were only detected in the heated MS after release with PNGase F. milks. A scalable purification process has also been developed to Other applications to glycan analysis in milk are listed in generate antibodies of high purity from glycoengineered Pichia Table 32. pastoris fermentation. Protein A affinity chromatography was used to capture the antibody from a fermentation supernatant and a pH gradient elution was applied to the column to prevent 2. Oligosaccharides in Beer antibody precipitation at low pH. The recovered antibody 2,4-DHB, 2,5-DHB, and 2,6-DHB at various of dilutions have contained some product-related impurities, which were removed been evaluated for analysis of oligosaccharides in four different by cation exchange chromatography with a NaCl gradient at brands of beer (Cass, Hite, Budweiser, Miller) (Park et al., pH 4.5–6.0. N-glycan profiles were monitored by MALDI-TOF. 2012a). No oligosaccharide ions were observed with 2,4-DHB, The antibody was comparable to its commercial counterpart in but it was found that 2,6-DHB was more effective than 2,5-DHB heterotetramer folding, physical stability, and binding affinity in most of the investigated concentration ranges. 2,6-DHB with (Jiang et al., 2011b). fourfold dilution was the most effective. An automated process for high-throughput profiling of N- MALDI-TOF MS with DHB as the matrix has been linked glycans in therapeutic antibodies using a microfluidic CD used to analyze beer from different sources by examining platform and MALDI-MS has been described (Thuy, Ingan€as, & the maltooligosaccharides and protein content. The maltooli- Thorsen, 2011). IgG1 was captured from a crude cell superna- gosaccharide profiles acquired from the center of the tant using protein A beads and the N-glycans were released with MALDI target were found to be uncharacteristic for beers PNGase F. Glycans were purified with a graphitized carbon from different sources. On the other hand, the protein black column, and both this stage and crystallization for profiles which were obtained from the periphery of the MALDI-TOF analysis were performed on the CD (Andersson target enabled the authors to distinguish beer samples of the et al., 2007; Thuy et al., 2010). same brand produced by different breweries. The method Tep et al. (2012b) have developed a method for looking at was tested on a set of seventeen lager beers, where the glycomic changes that occur in CHO cells other than those protein profiles enabled of majority of the brands to be associated with the expressed biotherapeutic. The method identified (Sedo, Marova, & Zdrahal, 2012). involved the lysing of cells to gain access to intracellular A method for recovery of glycoproteins and some other proteins after which, the expressed biotherapeutic was specifi- glyco-compounds from beer involves prior precipitation of cally removed by affinity chromatography. The remaining proteins with SDS followed by KCl and then addition of acetone glycoproteins were subjected to deglycosylation with PNGase F, to precipitate the glycoproteins (Mainente et al., 2011). the glycans were labeled with 12C- or 13C-2-AA and quantitative analysis was performed by MALDI-TOF MS in negative-ion 3. Biopharmaceuticals mode. A method for the localization of carbohydrate haptens in a This is another growing field with many new biopharmaceuticals Bacillus anthracis neoglycoconjugate vaccine using MALDI- containing glycans. Most of these compounds are recombinantly TOF MS and LC-ESI-tandem mass spectrometry has been expressed in various systems, many of which have been published by Jahouh et al. (2011). The vaccine consisted of the bioengineered to produce human-type glycosylation to avoid synthetic tetrasaccharide from B. anthracis linked via squaric glycan-induced allergic reactions. Predominant among these acid to a BSA protein carrier protein (107). Single-stage reactions are those caused by the presence of a-galactose MALDI-MS analysis of the glycoconjugate was carried out to substituents or N-glycoylneuraminic acid (5/38). Reviews of verify the average hapten-BSA ratio, which was found to be the topic are listed in Table 33 and applications are listed in 5.4:1. High-energy MALDI-MS/MS analysis was then per- Table 34. formed on GluC V8 endoproteinase digestion products to reveal Practical details for the determination of antibody glycosyl- glycation sites at Lys235,Lys420, and Lys498. Tryptic digests of ation based on PNGase F release and MALDI-TOF analysis and the conjugate yielded two additional glycation sites on Lys100 by ESI analysis of the glycans attached to the FC fragment of and Lys374. However, nano-LC-MS/MS analysis of the tryptic IgGs have been published in the Methods in Molecular Biology and GluC V8 digests yielded 30 sites. The use of GluC V8 series (J€ager et al., 2012). Details have also beem published for endoproteinase for the neoglycoconjugate digestion revealed

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TABLE 29. Use of MALDI MS for examination of carbohydrate-containing compounds in diseasea Disease Medium Methodsb Notes Reference Cancer Expression of GD3 synthase shown to modify ganglioside (Steenackers et Breast cancer MCF-7 cells TOF/TOF (DHB) profile and increases migration al., 2012a) of MCF-7 cells Difference in binding to PNGase F, FT-ICR Serum galectin-1 or galectin-8, may (Carlsson et al., Breast cancer (DHB), N-glycans haptaglobin provide biomarker. Related to 2012) (2-AA) triantennary glycan Human and PNGase F, FT-ICR High-mannose glycans elevated (de Leoz et al., Breast cancer mouse serum (DHB), N-glycans during cancer progression 2011) Trypsin, Q-TOF High-mannose, biantennary MCF-7 and T- (DHB, complex. N-glycan profile (Lattová et al., Breast cancer lymphoblastoid phenylhydrazine changes after Herceptin 2011) cells HCl) glycopeptides treatment Hyaluronans Hyaluronidase, Demonstrates overexpression of Breast and (Srinivas et al., from tissue MALDI (DHB), HA-hexa binding protein in stomach cancer 2012) samples glycans (2-AA) tumors Study of the role of 9-O-Ac- Childhood acute TOF (DHB), sialoglycoproteins in (Chowdhury et lymphoblastic Lymphoblasts Neu5Ac (DMB- mobilization of lymphoblasts al., 2012) leukaemia derivatives) from bone marrow to peripheral blood Identification of N-linked PNGase F, glycans as biomarkers - up- (Balog et al., Colorectal cancer Tissue TOF/TOF (DHB), regulation of paucimannosidic 2012) N-glycans (2-AA) glycans Membrane-type Detection by MALDI-MS of 1 matrix QIT-TOF (3- heterogeneous O-glycosylation (Shuo et al., Fibrosarcoma metallo-proteinase AQ/CHCA), MT1-MMP expressed in cancer 2012) from HT1080 peptides cells cells Heat-shock protein 27 shown to Gastrointestinal TOF (CHCA), be a target of methylglyoxal (Oya-Ito et al., Cancer cell lines cancer QIT-TOF (DHB) (glycolytic product) in 2011) gastrointestinal cancer Formalin-fixed, Prominent expression of sialyl β-Elimination, Gastric MALT paraffin- Lewis X-capped core 2-branched (Kobayashi et TOF/TOF, O- lymphoma embedded tissue O-glycans found on high al., 2011b) glycans (per-Me) and CHO cells endothelial venule-like vessels Differentiation of cancer and Serum PNGase F, QIT- Hepatocellular cirrhosis from hepatitis B (Zhang et al., haptoglobin β- TOF (DHB), N- carcinoma infection. Several glycan 2011f) chain glycans changes were diagnostic Differences in CD75s- and iso- CD75s-ganglioside content and Hepatocellular (Souady et al., Tissue lipids IR-TOF altered mRNA expression of carcinoma 2011) sialyltransferases ST6GAL1 and ST3GAL6 Development of quantitative Endo-H, endo-F2, Hepatocellular method based on 18O-labelling. (Zhang, et al., Serum R-QIT-TOF, N- carcinoma Bisected and biantennary 2011h) glycans glycans elevated. Differences in N-glycans, PNGase F, TOF Hepatocellular particularly sialylation levels (Kang et al., Serum (DHB), N-glycans carcinoma noted between cancer, cirrhosis 2011b) (per-Me) and controls. Hepatocellular PNGase F, L-TOF Use of mesoporous carbon for (Qin, et al., Serum carcinoma (DHB), N-glycans rapid glycan profiling 2011) Trypsin, TOF Fucosylation abnormalities used Hepatocellular (Liao et al., Serum (CHCA), to distinguish cancer from carcinoma 2012) glycopeptides controls PNGase F, CD98 and intercellular adhesion Hodgkin’s Hodgkin's Reed- (Powlesland, et TOF/TOF (DHB), molecule-1 shown to be carriers lymphoma Sternberg cells al., 2011) N-glycans (per-Me) of CD15/Lewis-x epitopes

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TABLE 29. (Continued) Human alveolar Lipids and gangliosides found to (García-Álvarez epithelial A549 cells TOF be altered in tumor cells treated et al., 2011) carcinoma with antimitotic oleyl glycoside LC-MALDI- Deglycosylation shown to reveal Serum tryptic (Toyama et al., Lung cancer TOF/TOF (CHCA, new glycopeptides (complement digest 2011) NH4Citrate) C9) PNGase F (in-gel), Sialylated triantennary glycan Serum TOF, Q-TOF with antenna-fucose elevated in (Tsai, et al., Lung cancer haptoglobin (DHB), ESI, N- cancer patients. Use to monitor 2011) glycans (per-Me) cancer progression PNGase F, Development of enrichment IgG from IgG- (Svoboda, et al., Lung cancer TOF/TOF (DHB), method, N-glycan analysis, high- depleted serum 2012) N-glycans (per-Me) mannose biantennary complex PNGase F, Identification of N-glycans in Ovarian Human SKOV3 TOF/TOF (DHB), total glycoprotein fraction. (Machado et al., carcinoma cells desialylated N- (high-mannose, bi-, tri-, tetra- 2011) glycans antennary complex) Increased tri- and tetra-antennary PNGase F, Ovarian complex, antennary fucose and (Alley et al., Human serum TOF/TOF (DHB), carcinoma α-Gal. Decreased bisecting 2012) N-glycans (per-Me) glycans in IgG Proteinase K, Identification of mono- and MALDI-MS/MS, disulfated N-acetyl-lactosaminyl Ovarian (Shibata et al., Cancer tissue LC-MS/MS, oligosaccharides as epitopes carcinoma 2012) glycopeptides (per- recognized by humanized Me) monoclonal antibody HMOCC-1 PNGase F, QIT Development of method and Pancreatic Serum (DHB), structural identification. Core (Lin, et al., cancer haptoglobin desialylated N- and antenna fucosylation 2011e) glycans (per-Me) elevated Bi-, triantennary complex. PNGase F, Identication of hyperfucosylated Pancreatic Pancreatic cyst (Mann et al., TOF/TOF (DHB), lactosamines on the N-linked cancer fluids 2012) N-glycans (per-Me) glycans of overexpressed glycoproteins Prostaglandin D2 synthase Pediatric Trypsin, TOF/TOF identified as putative biomarker. (Rajagopal et al., medullo- CSF (CHCA), N-glycan structures proposed but 2011) blastoma glycopeptides not confirmed Treatment with F-containing (Nishimura et al., Prostate cancer Human PC3 cells TOF GlcNAc mimics downregulated 2012) branched N-glycans Method development for 96-well PNGase F, TOF plate solid-phase methylation. (Jeong, et al., Prostate cancer Serum (DHB), N-glycans High-mannose, bi-, tri-antennary 2012b) (per-Me) complex Serum IgG Fc Trypsin, FT-ICR Increases in galactosylated and (Chen et al., Thyroid cancer (138 patients, (CHCA), sialylated glycans. Decrease on 2012b) 735 controls) glycopeptides G0F and bisected glycans Trypsin, PNGase Comparative studies on F, QIT-TOF (Mitsui et al., Various cancers Cells glycoproteins expressing (DHB), N-glycans 2012) polylactosamine-type N-glycans (2-AA) CDG Transferrin from Mutations at glycosylation site (Guillard et al., CDG Type I TOF (sinapinic) plasma found to complicate diagnosis 2011c) Serum PNGase F, TOF (Millón et al., CDG Type Ix Reduced sialylation transferrin (THAP), N-glycans 2011) Serum MALDI -linear ion (Guillard et al., CDG Type II β-Galactosidase deficiency transferrin trap 2011b) Complex bi-, tri-, terta- PNGase F, TOF, Serum antennary. Slightly more G0 (Foulquier et al., CDG Type II N- and O-glycans glycoproteins structures in patients. Caused by 2012) (per-Me) deficiency in TMEM165 Serum Reduction of sialylation on N- (Fung et al., COG5-CDG TOF, N-glycans transferrin glycans 2012)

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TABLE 29. (Continued) Deficiency of subunit 6 of Golgi Serum TOF, N- and O- (Huybrechts et COG6-CDG complex. Low sialylation and transferrin glycans al., 2012) galactosylation Serum Mutation in dolichol-phosphate- (Barone et al., DPM2-CDG TOF, N-glycans transferrin mannose synthase 2012b) Epithelial PNGase F, R- membrane Classical galactosemia shown to TOF/TOF (DHB), (Staubach et al., Galactosemia glycoproteins produce shifts toward complex- N-glycans (Per- 2012) from urinary type N-glycosylation Me) exovesicles N-, O-glycans normal. Missense Serum mutation detected in DDOST (Jones et al., Untyped TOF transferrin involved in glycan transfer from 2012a) lipid carrier to protein Arthritis N-Glycanase, Alterations in the levels of high- Human and TOF/TOF (DHB, mannose glycans accompany (Urita et al., Osteroarthritis mouse cartilage CHCA), N-glycans arthritis. Increased GlcNAc 2011) ( 2-AP), HPLC transferase activity No association found between Rheumatoid Trypsin, TOF, (van de Geijn et Serum mannose-binding lectin, disease arthritis glycopeptides al., 2011) activity or IgG galactosylation Endo H, R- Use of endo H to release high- Rheumatoid TOF/TOF (s- (Frisch et al., Serum mannose and hybrid glycans. arthritis DHB), N-glycans 2011) Little difference from controls (per-Me) Test of efficiency of plant- Rheumatoid PNGase F, TOF (Alavi et al., Serum derived polysaccharide arthritis (DHB), N-glycans 2011) supplement Other Adverse (Amigo- immune TOF (CHCA), To study mechanism of allergic In vitro digestion Benavent et al., reactions to peptides response 2011) soybean As reference for development of Serum TOF (CHCA), Alcohol abuse capillary isoelectric focusing (Luo et al., 2011) transferrin glycoprotein assay PNGase F, TOF Amyotrophic High levels of sialylated glycans (Edri-Brami et Serum IgG Fc (DHB), N-glycans lateral sclerosis and low core fucosylation al., 2012) (2-AB), HPLC Autoimmune Treatment with GlcNAc PNGase F, TOF encephalo- increased branching of N- (Grigorian et al., CD3+ T cells (DHB), N-glycans, myelitis glycans suggesting oral GlcNAc 2011) HPLC (experimental) as treatment Autosomal Method for analysis of mucin- recessive cutis ApoCIII from TOF (DHB), type glycosylation. (Wada et al., laxa type-2 serum glycoprotein Demonstrated decreased site 2012) (ARCL2) occupancy in patients Brain PNGase F, TOF N-glycan profiles to investigate (Fogli et al., developmental CSF (DHB), N-glycans biomarkers 2012) disorders (per-Me), PSD Endopeptidase, Deficiency of N- IgA hinge trypsin, TOF acetylgalactosamine in O-linked (Inoue et al., Crohn’s Disease glycopeptides (DHB), glycans of IgA found to be a 2012) from serum glycopeptides novel biologic marker Tamm-Horsfall TOF (s-DHB), N- Large increase found in tetra- (Parsons et al., Cystitis protein from glycans (per-Me), sialylated glycan in patients 2011) urine HPLC (2-AB) compared with controls Discussion of the use of glycated (Lapolla et al., Diabetes Haemoglobin MALDI haemoglobin for diagnosis 2011a) Vanadium, administered orally (Iglesias- Transferrin in rat as bis(maltolato)oxovanadium Diabetes TOF González et al., serum (IV) shown to bind to serum 2012) transferrin Streptozotocin- Four glycated proteins found to (Chougale et al., Diabetes induced diabetic Q-TOF (DHB) be up-regulated 2012) rat kidney

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TABLE 29. (Continued) Familial Protein glycation of plasma (da Costa, et al., amyloidotic Fibrinogen TOF/TOF (CHCA) proteins shown to be a factor 2011) polyneuropathy PNGase F (for N- Infants with classic galactosemia Plasma linked), β-elim. demonstrated galactose- glycoproteins (for O-linked), R- (Liu et al., Galactosemia dependent aberrant N- and O- (infants, TOF/TOF (DHB), 2012j) linked protein glycosylation but children, adults) N-O-glycans (per- adults did not Me) Bi-, tri-antennary complex. Gestational Glycodelin-A PNGase F, Reduced α2-6 sialylation and (Lee et al., diabetes from human TOF/TOF (DHB), impaired immunomodulatory 2011b) mellitus amnionic fluid N-glycans (per-Me) activity of pregnancy-related glycodelin-A Gammopathy with IgA PNGase F, TOF, Hyposialylation of biantennary (Boumediene et IgA mesangial N-glycans glycans al., 2011) deposition Granulomatosis PNGase F, TOF, Biantennary complex glycans. with (Espy et al., Serum IgG N-glycans (per- Sialylation levels lower in polyangiitis 2011) Me) patients with disease (Wegener’s) Identification of biantennary Idiopathic PNGase F, TOF, Serum glycans terminating in GlcNAc (Futakawa et al., normal pressure QIT-TOF (DHB), transferrin with core fucose and bisecting 2012) hydrocephalus N-glycans (2-AP) GlcNAc. Possible biomarkers PNGase F (for N- IgA IgA1 and soluble Both diseases feature abnormally linked), β-elim. nephropathy CD89–IgA and glycosylated IgA1 complexes. (Tissandié et al., (for O-linked), and alcoholic IgG–IgA Galactose deficiency and 2011) TOF, N-, O- cirrhosis complexes decreased sialylation glycans (per-Me) Quantitative change of IgA Trypsin, TOF hinge O-glycan composition IgA (Iwatani et al., Serum (DHB), found to be marker of nephropathy 2012) glycopeptides therapeutic responses of IgA nephropathy Study suggests link between kidney dysfunction and hepatic (Sheng et al., Kidney injury Serum TOF, sulfatides sulfatides metabolism mediated 2012) by oxidative stress Rabbit skeletal Hyperphosphorylation of (Tagliabracci et Lafora disease TOF (THAP) muscle glycogen glycogen shown to cause disease al., 2011) Lambert-Eaton Disease showed lower levels of myasthenic Trypsin, FT-ICR IgG1 and IgG2 galactosylation. Patients under (Selman et al., syndrome and (CHCA), Fc (N-glycans) 50 years old showed elevated 2011b) myasthenia glycopeptides bisecting GlcNAc gravis PNGase F, R-TOF, Alterations of serum protein N- Serum proteins (Blomme, et al., Liver disease TOF/TOF (DHB), glycosylation shown to be (mouse) 2011) N-glycans (per-Me) hepatocyte and not B cell driven PNGase F, R-TOF, Separation of liver-secreted and Serum (Bekesova et al., Liver disease TOF/TOF (DHB), IgG-derived N-glycans to detect glycoproteins 2012) N-glycans (per-Me) cirrhosis Disialo-trisialo bridging of Serum PNGase F, TOF transferrin shown to be due to (Landberg et al., Liver disease transferrin (THAP), N-glycans increased branching and 2012) fucosylation of the N-glycans Peripheral blood Genetics and the environment Multiple (Mkhikian et al., mononuclear TOF, N-glycans both act to dysregulate N- sclerosis 2011) cells glycosylation Search for biomarker. Salivary FTICR (DHB), N- (Vieira et al., Ocular rosacea Tears and saliva N-glycans fucosylated, tear glycans 2012) glycans sulfated Use of specific transferrin Serum Ryegrass TOF/TOF, Intact enrichment by immuno-capture (Penno et al., transferrin from toxicity glycoprotein with functionalized magnetic 2012) rats beads aHuman unless otherwise stated. bFormat (not all items present): Glycan release method and/or protease, MALDI method (matrix), compounds run (derivative), other methods.

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TABLE 30. Reviews and general articles on the application of MALDI to disease Subject Citations Reference Protein profiling for cancer biomarker discovery 78 (Bakry et al., 2011) Glycomics of pediatric and adulthood diseases of the central nervous system (Barone et al., 106 (CNS) 2012a) Use of matrix-assisted laser desorption/ionisation mass spectrometry in cancer (Bateson et al., 65 research 2011) Mass spectrometric methods for antibody characterization 39 (Beck et al., 2012) (Goreta et al., Insights into complexity of congenital disorders of glycosylation 90 2012) Recent developments in analytical methods for biomarker discovery 88 (Hua & An, 2012) Glycans as biomarkers: Status and perspectives 138 (Janković, 2011) Mass spectrometry-based approaches to study properties and behavior of protein (Kaltashov et al., 101 therapeutics 2012) Recent advances in the electrophoresis of mucins - application to cancer cell (Kameyama & 39 lines Matsuno, 2012) (Kim & Misek, Glycoproteomics-based identification of cancer biomarkers 116 2011) Expression level and glycan dynamics determine the net effects of TIMP-1 on 51 (Kim et al., 2012g) cancer progression (Lapolla et al., Some views on proteomics in diabetes 80 2011b) Application of glycoproteomics for the discovery of biomarkers in lung cancer 90 (Li et al., 2012e) (Mechref et al., Defining putative glycan cancer markers by mass spectrometry 61 2012b) Identification of cancer biomarkers by mass spectrometry-based glycomics (Mechref et al., 73 (mainly N-glycans; MALDI and LC/MS) 2012a) (Morava et al., Protein glycosylation and congenital disorders of glycosylation 63 2011) Mass spectrometry based glycoproteomics-from a proteomics perspective 216 (Pan et al., 2011a) (mainly biomarkers) Glycoengineered glycan sensors to enable native glycoprofiling for medicinal 208 (Reuel et al., 2012) applications The impact of mass spectrometry in the diagnosis of congenital disorders of (Sturiale et al., 63 glycosylation 2011a)

12 13 more carbohydrate haptens occupancies and their respective amination with either [ H7]- or [ H7]- 2-AA and mixed in glycation sites than when only trypsin was used. The authors equal proportions. The results were monitored by MALDI-TOF preferred the ESI-CID-MS/MS approach because MALDI-CID MS. The method was reported to display a linear dynamic range fragmentation yielded many additional fragment ions from the over two orders of magnitude with sub-picomolar sensitivity and glycan, which complicated the spectra. was applied to the analysis of Fc-fusion protein (mainly A method has been described for quantitative comparison biantennary N-glycans). of neutral and sialylated glycans from Chinese hamster ovary MALDI-TOF has been used to conﬁrm the presence of (CHO)-expressed glycoproteins (Tep et al., 2012a). Glycans Con-A on RNase B-modiﬁed gold nanoparticles used for were released with PNGase F and derivatized by reductive probing glycosylation of glycoproteins (Sanchez-Pomales et al.,

HO CH3 O O NH NH Carrier CH O HO 3 HO NH HO CH3 O O O O O OO H3C O O NH HO HO OCH3 HO

H3C HO CH3

107

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TABLE 31. Use of MALDI to study enzyme reactions Enzyme Source Instrumenta Notes Reference Glycosyltransferases Arabidopsis GUX Enzymes shown to be Expressed in (Lee et al., proteins (glucuronyl- TOF (DHB) responsible for addition of tobacco BY2 cells 2012c) transferases) GlcA side chains onto xylan Glycosyl transferases in α-(1,3)- TOF, glycans family 61 shown to mediate (Anders et al., Wheat endosperm Arabinosyltransferase (2-AA) Araf transfer onto xylan in 2012) grasses Endo-1→3-β-D- Tapes literata TOF/TOF Catalytic properties and (Zakharenko et glucanase (marine mollusc) (DHB) amino acid sequence al., 2012) Study of reaction conditions Fructosyltransferase Aspergillus R-TOF (Montilla et al., on oligosaccharide synthesis (Pectinex Ultra SP-L) aculeatus (DHB), GLC 2011) from stachyose Caenorhabditis TOF/TOF Enzymes from distantly elegans (FUT-1) (DHB, related plants and α1,3- (Both et al., and Arabidopsis CHCA), nematodes display similar Fucosyltransferases 2011) thaliana FucTA glycans, trends in structure–function (FUT11) glycopeptides relationships Fucosyltransferase Caenorhabditis R-TOF Study of mechanism of (Lira-Navarrete POFUT1 elegans (CHCA, -ve) protein O-fucosylation et al., 2011) Enzyme mediates Galactosetransferase Mycobacterium (May et al., TOF bifunctional catalysis using GlfT2 tuberculosis 2012) a single active site (Rodriguez- Kluyveromyces TOF/TOF Study of transglycosylation β-Galactosidase Colinas et al., lactis (DHB) properties 2011) Elucidation of the sugar recognition ability of the TOF (DHB), (Yoshimura et GalNAc-transferase 3 Human lectin domain of UDP- ETD al., 2012c) GalNAc:polypeptide GalNAc transferase 3 Novel evolutionary R-TOF 4,6-α- Lactobacillus intermediate between the (Kralj et al., (DHB), Glucanotransferase reuteri 121 GH13 and GH70 enzyme 2011) GC/MS families Produced series of novel 4,6-α- Lactobacillus QIT-TOF (Dobruchowska linear iso-malto-/malto- Glucanotransferase reuteri 121 (DHB) et al., 2012) oligomers up to DP >35 Pseudomonas R-TOF aeruginosa PAO1, (DHB), Enzymes shown to transfer P. putida KT2440 glycans (-OH), (Hreggvidsson et β-Glucosyltransferases β-glucan donor to β-glucan and Azotobacter ESI-MS/MS, al., 2011) acceptor. vinelandii ATCC glycans (per- BAA-1303 Me) Shown to be an inverting Actinobacillus enzyme that recognizes the (Schwarz et al., N-Glycosyltransferase TOF pleuropneumoniae NX(S/T) N-glycan 2011a) consensus sequence Sublancin transferase from Study of substrate (Wang & van der S-Glycosyltransferase TOF, ESI Bacillus subtilis specificity Donk, 2011) 168 First report of a Glycosynthase derived glycosynthase that employs (Ohnuma et al., from an inverting Bryum coronatum TOF (DHB) amino sugar fluoride as a 2012) GH19 chitinase donor substrate Study of enzyme specificity. Pasteurella (Otto et al., Heparosan synthases R-TOF (ATT) Production of novel multocida 2012) catalysts Dystroglycan function LARGE (like- shown to require xylosyl- (Inamori et al., acetylglucosaminyl- In HEK293 cells MALDI and glucuronyl-transferase 2012) transferase activities of LARGE

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TABLE 31. (Continued) Shown to have the same Maltosyltransferase Streptomyces catalytic properties as (Syson et al., TOF GIgE coelicolor Mycobacterium tuberculosis 2011) GlgE R-TOF/TOF Bacterial enzyme for N- Oligosaccharyl- Campylobacter (DHB), (Schwarz et al., glycosylation of proteins. transferase jejuni glycans (per- 2011b) Relaxed substrate specificity Me) First characterization of an R-TOF/TOF, OTase from Desulfovibrio (Ielmini & PglB glycol- deltaproteobacteria involved desulfuricans Feldman, 2011) peptides in N-linked protein glycosylation Polypeptide GalNAc- Human cell line TOF, Functions of individual (Schjoldager et transferases “SimpleCells” glycopeptides transferases al., 2012) R228K-Y289L-β4Gal- The N-Ac-binding pocket of T1 mutant, wild-type GlcNAc transferases shown (Pasek et al., β Human and mutant L-TOF (DHB) to accommodate a sugar human 1,3-GlcNAc 2012) transferase-2 and analog with chemical handle human Maniac Fringe at C2 Trypsin, R- Toxin A Clostridium TOF/TOF Structure and function. (Pruitt et al., glucosyltransferase difficile (CHCA), Substrate specificity 2012) glycopeptides Enzymes expressed in a UDP-galactose: β-D- species-specific manner and α β Pigeon, ostrich and TOF (DHB) (Suzuki et al., galactoside (and ) are distributed throughout 1,4-galactosyl- chicken glycans (2-AP) 2011b) the entire body of pigeon or transferase ostrich. TOF (DHB), GT43 enzymes shown to be Xylan Arabidopsis (Lee et al., glycans (2- required for elongation of xylosyltransferases thaliana 2012a) AA) xylan backbone Populus Xylan TOF, glycans Characterization of enzymes (Lee et al., trichocarpa xylosyltransferases (2-AA) involved in wood formation 2012b) (Poplar) Substrate specificity and β1,2- Arabidopsis participation in plant- (Kajiura et al., TOF Xylosyltransferase thaliana specific N-glycosylation 2012) pathway Glycosidases α-N-acetyl- (Mrázek et al., Aspergillus niger TOF (CHCA) Production in yeast galactosaminidase 2012) Persicobacter sp. (Han et al., Agarose depolymerase TOF Isolation and identification JZB09 2012c) Study of transglycosylation (Mótyán et al., α-Amylase Barley R-TOF (DHB) activity 2011) Zobellia 1,3-α-3,6-Anhydro-L- MALDI to characterize (Rebuffet et al., galactanivorans TOF (DHB) galactosidase reaction products 2011) (marine bacterium) Bifidobacterium Cloning and (Fujita et al., β-L-Arabinobiosidase TOF (DHB) longum characterization 2011a) Arabinoxylan-specific Clostridium TOF (DHB/1- (Correia et al., Structure and function xylanase thermocellum HIQ), ESI 2011) Baculovirus envelope Autographa Chondroitinase with distinct (Sugiura et al., protein ODV-E66 californica nucleo- TOF substrate specificity. Useful 2011) (chondroitinase) polyhedrovirus for analysis First report of a BcChi-A (GH19 Bryum coronatum glycosynthase that employs (Ohnuma, et al., TOF (DHB) chitinase) (moss) amino sugar fluoride as a 2012) donor substrate C1 α-L- Chrysosporium Identification of mode of (Kühnel et al., MALDI Arabinohydrolases lucknowense action 2011) The cellulose-binding Cellobiohydrolase TOF (Hall et al., Trichoderma reesei domain shown to be a Cel7A (sinapinic) 2011) thermostabilizing domain

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TABLE 31. (Continued) CfcI, glycoside Shown to release monomers (van Munster et hydrolase family 18 Aspergillus niger TOF (DHB) during substrate hydrolysis al., 2012) chitinase Autographa Purification from Sf-9 (Fukamizo et al., Chitinase TOF (DHB) californica medium and mode of action 2011) Bacillus cereus (Wang et al., Chitinase TOF (DHB) Purification and function TKU027 2012f) Serratia Study of substrate (Norberg et al., Chitinase A TOF marcescens positioning 2011) Catalytic amino acid (Martinez et al., Chitinase A1 Bacillus circulans TOF (DHB) mutations convert enzymes 2012) to transglycosylases Catalytic amino acid Trichoderma (Martinez, et al., Chitinase 42 TOF (DHB) mutations convert enzymes harzanium 2012) to transglycosylases Bacillus subtilis TOF/TOF Characterization of (Kang et al., Chitosanase HD145 in Pichia (DHB) expressed enzyme 2012b) pastoris Production and purification Bacillus cereus (Liang et al., Chitosanase TOF (DHB) of a protease, a chitosanase, TKU022 2012b) and chitin oligosaccharides TOF/TOF Aspergillus (sinapinic for Characterization. Degrades (Hirano et al., Chitosanase II fumigatus protein, DHB GlcN mainly to GlcN 2012) ATCC13073 6 3 for glycans) Chitotriosidase (family R-TOF/TOF Mechanism of action - (Eide et al., Human 18 chitinase) (DHB) endoprocessive 2012) MALDI to characterize (Ohnuma et al., Class V chitinase Nicotiana tabacum TOF (DHB) reaction products 2011a) Arabidopsis MALDI to characterize (Ohnuma et al., Class V chitinase TOF (DHB) thaliana reaction products 2011b) Overexpression in DagA (endo-type β- Streptomyces Streptomyces lividans and (Temuujin et al., TOF agarase) coelicolor A3(2) biochemical 2011) characterization Shown to hydrolyse high- Endo-β-N- Enterococcus (Bøhle et al., TOF (DHB) mannose and hybrid N- acetylglucosaminidase faecalis V583 2011) glycans Endo-β-N-acetyl- Bifidobacterium FT-ICR Shown to release N-glycans (Garrido, et al., glucosaminidase (endo infantis ATCC (DHB), from human milk 2012) BI-1) 15697 glycans glycoproteins Endo-1,3-β-D- TOF (DHB), From Vietnamese edible (Zakharenko et Perna viridis glucanase ESI mussel al., 2011) Practical methods to Endo-β(1→4)- TOF (DHB), (Eklöf et al., Various plants determine xyloglucanase glucanase ESI 2012) activity Shown to be a metal- Endoglucanase Phanerochaete (Westereng et TOF dependent oxidative enzyme PcGH61D chrysosporium al., 2011) that cleaves cellulose Used to prepare core- Endoglycosidases Flavobacterium TOF (DHB, (Huang et al., fucosylated complex N- Endo-F2 and Endo-F3, meningosepticum CHCA) 2011c) glycans Endo-β-1,4- Produced in Pichia pastoris Aspergillus R-TOF/TOF (Dilokpimol et mannanases X33. Show different trans- nidulans FGSC A4 (DHB) al., 2011) (two enzymes) glycosylation capacity Bacteroides TOF/TOF thetaiotaomicron Structural and mechanistic (DHB), (Thompson et Endo-α-mannosidase (BtGH99) and B. studies of N-glycan glycans (per- al., 2012) xylanisolvens processing Me) (BxGH99) R-TOF Exo-β-(1→3)-D- (DHB), Useful for probing type II (Ling et al., Streptomyces sp. galactanase glycans (per- arabinogalactan structure 2012) Me) Extracellular β-D- Penicillium Isolation and (Dubrovskaya et TOF (DHB) glucosidase canescens characterization al., 2012)

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TABLE 31. (Continued) Characterization of a Family 31 α- Cellvibrio TOF (DHB), glycoside hydrolase (Larsbrink et al., xylosidase japonicus LC/MS involved in xyloglucan 2011) saccharification Fusarium Identification of α- oxysporum strain (Paper et al., α-Fucosidases TOF fucosidases with different 0685, F. 2012) substrate specificities graminearum TOF (DHB for Investigation of causes of Bacillus circulans glycans, (Song et al., β-Galactosidase multiple forms in a ATCC 31382 sinapinic for 2011a) commercial preparation proteins) Binding of GlcNAc-1→6- branched oligosaccharide (Ramakrishnan β1→4-Galactosidase I Commercial TOF acceptors revealed a new et al., 2012) ligand binding mode TOF/TOF, Investigation of metabolism Galactosidases (family Ruminococcus (Cervera-Tison glycans (per- of a plant oligosaccharide GH36) gnavus E1 et al., 2012) Me), ESI by a human gut symbiont α-Galactosidase/ TOF Bifunctional enzyme with (Bruel et al., sucrose kinase Human (DHB/N,N- galactosidase and kinase 2011) (AgaSK) DMA) activities Characterization and Thermoplasma (Seo et al., α-Glucosidase TOF transglucosylation reaction acidophilum 2011b) with arbutin Glucuronoxylan- Paenibacillus Identification and (Valenzuela et TOF (DHB) specific xylanase barcinonensis characterization al., 2012) Production in Production by lyase (Barreteau et al., Heparosan engineered E. coli TOF, ESI expression 2012) K-12 Hydrolase acting on Streptomyces Acts synergistically with (Forsberg et al., TOF cellulose coelicolor cellulases 2011b) Role of the subsite +2 in β-Mannanase (Rosengren et Trichoderma reesei TOF (DHB) hydrolysis and TrMan5A al., 2012) transglycosylation Four mannosidases Caenorhabditis TOF/TOF α1,2-Mannosidases expressed and activity (Wilson, 2012) elegans (ATT) determined Human In vitro mannose trimming (Aikawa et al., α-1,2-Mannosidase 1 endoplasmic TOF property 2012) reticulum Thermotoga Molecular cloning and (Kang et al., Pullulanase, Type I TOF neapolitana characterization 2011a) TOF/TOF Use for transglycosidases α-Rhamnosyl-β- Acremonium sp. (Minig et al., (DHB, nor- reactions with rutinose to glucosidase DSM 24697 2011) harmane) confer aroma to food Sco3487 (endo-type Streptomyces Isolation and (Temuujin et al., TOF β-agarase) coelicolor A3(2) characterization 2012) Enzyme shown to have N- Serotype 4b autolysin Listeria TOF (CHCA) (Ronholm et al., acetyl-glucosaminidase IspC monocytogenes muropeptides 2012) activity (Kumar & Bacillus Isolation and substrate Xylanase TOF Satyanarayana, halodurans specificity 2011) Xylanase from Advantages of isothermal Recombinant in (Baumann et al., Aspergillus aculeatus TOF titration calorimetry for Aspergillus oryzae 2011) (Aac–Xyn) xylanase kinetics Nasturtium Xyloglucan TOF (DHB), Effect of fluorescent label (Kosík et al., (Tropaeolum endotransglycosylase ISD on kinetic parameters 2011) majus) seeds R-TOF/TOF Involved mainly in the Xyloglucan (2,5- restructuring of the cell wall (Miedes et al., Tomato endotransglycosylase dihydroxy- during growth and 2011) cinamic acid) development. AtBGAL10 Shown to be the Xyloglucan β- Arabidopsis TOF/TOF (Sampedro et al., main Xyl-β-galactosidase in galactosidase thaliana (DHB) 2012) Arabidopsis

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TABLE 31. (Continued) Xyloglucan-specific Streptomyces Identification and (Enkhbaatar et family 74 endo-β-1,4- TOF coelicolor A3(2) characterization al., 2012) glucanase Thermobifida fusca Purification and (Fekete & Kiss, β-D-Xylosidase TM51 (recom- TOF characteristion 2012) binant in E. coli) Other hydrolases Turbo Catalyses cleavage of (Pesentseva et Aryl sulfatase chrysostomus TOF sulphate from the C4 al., 2012) (marine mollusc) position of xylose Phosphoglucan Arabidopsis Enzyme shown to (Santelia et al., R-TOF (DHB) dephosphorylate starch at phosphatise LSF2 thaliana 2011) the C3-position Other enzymes acting on sugars N-acetylglucos- Enzymes shown to be aminidase Acm2 and Lactobacillus TOF (for (Rolain, et al., pivotal in the physiology of the γ-D-Glu-mDAP plantarum WCFS1 muropeptides) 2012) L. plantarum. muropeptidase LytA Chrysosporium Characterization and mode (Pouvreau et al., Acetyl xylan esterases TOF lucknowense C1 of action 2011) Agarose depolymerases Flammeovirga sp. TOF (“Formic Characterization of (Han et al., (4) MY04 acid”) extracellular agarase system 2012d) Biochemical characterization and relative Prevotella (Kabel et al., Carbohydrate esterases L-TOF/TOF expression levels of enzyme ruminicola 23 2011) grown on an ester-enriched substrate Extraction of cellulose- Cellulose synthesizing Gluconacetobacter (Hashimoto et TOF (DHB) synthesizing activity with enzymes xylinus al., 2011a) alkylmaltoside The chbG gene of the (Verma & Chitooligosaccharide TOF/TOF Escherichia coli chitobiose (chb) operon Mahadevan, deacetylase (CHCA) shown to encode enzyme 2012) CMP-N- Stable co-expression of acetylneuraminic acid Human in tobacco L-TOF (DHB), enzymes in plant (Kajiura et al., (Neu5Ac) synthase cells glycans (2-AP) suspension-cultured tobacco 2011) (hCSS) and α2,6- cells sialyltransferase Study of action on large Aspergillus feruloyl-arabino-xylo- (Debeire et al., Feruloyl esterase TOF (DHB) nidulans oligosaccharides from wheat 2012) bran Bifunctional Comamonas glycosyltransferase (Otto et al., GAG synthase R-TOF (ATT) testosteroni producing a unique 2011) heparosan polysaccharide Glucocerebrosidase Cryptococcus TOF (DHB), Investigation of GlcCer (Ishibashi et al., EGCrP1 neoformans TLC catabolism 2012) β-endo- Methyltransferases Glucuronoxylan Arabidopsis (Lee et al., xylanase M6, catalyzing 4-O-methylation methyltransferases thaliana 2012d) TOF (DHB) of GlcA on xylan Pneumococcal Streptococcus MALDI to study peptidoglycan TOF (CHCA) (Bui et al., 2011) pneumoniae deacetylation of GlcNAc deacetylase PgdA Identification of enzyme Glycoside Rhizobium sp. (Kim et al., TOF (DHB) that deglycosylate oxidoreductase strain GIN611 2012d) ginsenosides Involvement in the TOF (DHB), Human natural biosynthesis of GlcUA(3-O- (Hashiguchi et Sulfotransferase glycans (2- killer-1 cells sulfate)-Gal-Gal-Xyl from al., 2011) AB) urinary α-thrombomodulin Expressed as recombinant Trans-sialidase TS1 Trypanosoma (Koliwer-Brandl TOF (DHB) proteins, and assayed for variants congolense et al., 2011) trans-sialylation activity. Study of the origin and UDP-L-Arabino- functions of (Konishi & Ishii, Rice TOF pyranose mutase arabinofuranosyl residues in 2012) plant cell walls aFormat (not all items present): MALDI method (matrix), compounds studied (derivative) other methods.

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TABLE 32. Use of MALDI-MS for the characterization of carbohydrates from milk and milk products Source Methodsa Glycans Notes Reference Bovine (Danish Mass and Comparison of glycan profiles. Jersey and FT-ICR monosaccharide Jersey milk found to contain higher (Sundekilde et Holstein- (DHB), LC/MS composition levels of fucosylated glycans and al., 2012) Friesians) only more complex structures DFpLNH II and LEISD-FT- Development of LEISD method (see (Yang, et al., Human milk DFLNnH ICR (DHB) text) 2011c) (octasaccharides) FT-ICR Identification of over 70 sialylated Human milk Sialylated (Wu et al., (DHB), glycans. Structure by HPLC-Chip/Q- oligosaccharides glycans 2011) exoglycosidase TOF MS. An infant-associated bacterial Human milk Sialylated (Sela et al., FT-ICR commensal shown to use breast milk oligosaccharides glycans 2011) sialyloligosaccharides Human milk TOF/TOF Study of factors affecting the growth (Rockova et Oligosaccharides oligosaccharides (DHB) of bifidobacteria in milk al., 2011) Complex milk oligosaccharides Human milk attract both mutualistic mucus- (Marcobal et FT-ICR Oligosaccharides oligosaccharides adapted bacteria and HMO-adapted al., 2011) bifidobacteria to the infant intestine. Human milk LTQ Orbitrap (Rohmer, et Free and 3-AQ Comparison of fragmentation modes oligosaccharides (harmine) al., 2011) Human milk R-TOF/TOF Rapid method for Lewis blood group (Blank, et al., Oligosaccharides oligosaccharides (ATT) assignment 2011) R-TOF/TOF Di-Fuc-iso-lacto- Development of a method for (ATT, CHCA), N-octaose and Human milk structural analysis of high molecular (Blank, et al., glycans (2-AB, tri-Fuc, doubly oligosaccharides weight oligosaccharides and 2012b) free and per- branched lacto- identification of new compounds. Me) N-neo-decaose Lacto-N-tetraose, fucosylation, and Human milk (De Leoz et FT-ICR (DHB) Oligosaccharides secretor status shown to be highly oligosaccharides al., 2012) variable in women delivering preterm Disialyllacto-N-tetraose prevents (Jantscher- Human milk TOF (s-DHB), Oligosaccharides necrotising enterocolitis in neonatal Krenn et al., oligosaccharides glycans (2-AB) rats 2012) Bifidobacterium longum subsp. Human milk infantis ATCC 15697 α-fucosidases (Sela et al., FT-ICR (DHB) Oligosaccharides oligosaccharides shown to be active on fucosylated 2012) human milk oligosaccharides Human milk TOF/TOF, (Yu et al., Oligosaccharides Array to study binding to viruses etc. oligosaccharides exoglycosidase 2012f) Proteomic approach to detect Milk protein TOF Lactosylated (Le et al., lactosylation and other chemical concentrate (sinapinic) proteins 2012) changes in stored protein concentrate Red kangaroo Sialylated and Structural determination. Acidic (Macropus rufus) R-TOF/TOF sulfated tri- to (Anraku et al., versions of carbohydrates found in acidic (DHB) branched 2012) tammar wallaby milk oligosaccharides heptasaccharides Shows that primate milk FT-ICR oligosaccharides do not necessarily (Tao et al., Various primates (DHB), Free glycans cluster according to the primate 2011) IRMPD phylogeny aFormat (not all items present): MALDI method (matrix), other methods, compounds analyzed.

2012). RNase B and the therapeutic monoclonal antibody unique optical reporting properties of gold nanoparticles, a (mAb) rituximab were found to adsorb spontaneously and non- glycosylation pattern of rituximab was generated. specifically to bare gold nanoparticles such that the glycans Fania et al. (2011) have investigated methods for monitor- were accessible for lectin binding. Addition of a multivalent ing erythropoietin in serum. A major problem was the large binding lectin, such as Con A, to a solution of the modified gold variations in protein abundance, which imposed a major nanoparticles resulted in cross-linking of the nanoparticles limitation hampering the identification of less abundant species within 1 min. By combining the sugar-binding specificity and and decreasing the quality of MALDI profiling. Two commer- the cross-linking capabilities of a variety of lectins, the non- cially available immunodepletion columns (MARS Hu7 and specific adsorption of glycoproteins to gold surfaces and the Hu14) were investigated for the removal of the more abundant

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TABLE 33. Reviews to the application of MALDI to the production of biopharmaceuticals Subject Citations Reference (Lingg et al., Importance of recombinant protein glycosylation analysis 99 2012) Development of methods for detecting minor amounts of α-Gal and Neu5Gc in (Maeda et al., 45 monoclonal antibodies 2012) Glyco-engineering of Fc glycans to enhance the biological functions of therapeutic (Raju et al., 96 IgGs 2011) (Raymond et Production of highly sialylated monoclonal antibodies 48 al., 2012) (Spearman et Role of glycosylation in therapeutic antibodies 213 al., 2011)

proteins and it was concluded that use of Hu14 is an efficient A. Synthesis of Multivalent Carbohydrates, and effective method for monitoring disease progression. Two Dendrimers, and Glycoclusters MALDI matrices, CHCA and 20,40-DHBP, were compared and the latter matrix was shown to give the best results. Analysis of glycodendrimers is one of the most challenging areas related to glycan synthesis as the mass of these compounds can often exceed 50 kDa. Syntheses frequently involves XXII. CARBOHYDRATE SYNTHESIS Huisgen-type click chemistry because high-yield reactions are This section is included to demonstrate the large range of essential when so many carbohydrate molecules have to be carbohydrates and carbohydrate-related compounds that can be attached. Table 39 lists compounds of this type that have been analyzed by MALDI. However, it is more difficult to obtain an analyzed by MALDI. Globular glycofullerenes containing 24 mannose resu- accurate picture of the application of MALDI in this area 108 because, as the tables show, few investigators report the dues ( ) have been prepared by (Sanchez-Navarro et al. conditions used for obtaining the spectra; statements such as (2011). Their MALDI-TOF mass spectra did not contain the “HRMALDIMS” seem to suffice. Failure to report the matrix, or molecular ion peak because of extensive fragmentation. the resolution used, is particularly widespread. In a few other However, analysis of the acetylated derivative of the compound with 12 mannose residues was successful, giving cases, details are reported in the general methods section, but þ þ then all of the synthesized products specify ESI as the method the molecular ion peak at m/z 7130 ([M H] calculated for used. A further complication is the use of “a combined MALDI/ C330H360N36O144). ESI source” with no indication of which method was employed; High molecular weight polyrotaxanes are usually char- these papers are not included. Not all attempts to obtain spectra acterized by NMR and size exclusion chromatography but are successful; for example, Przybylski and Jarroux (2011) rarely by MS. Przybylski, Blin, and Jarroux (2011) have report that MALDI-TOF failed in an analysis of polydisperse investigated the use of MALDI-TOF MS for this purpose with particular attention being given to verification of the polyrotaxane based on poly(ethylene oxide) and a-cyclodextrins 109 although nanoelectrospray was successful. Reviews on synthesis number of macrocycles borne by polyrotaxanes such as . involving MALDI analysis are listed in Table 35. Compounds Various matrices including crystalline or ionic liquids were synthesized are listed in Table 36, synthetic methods are in Table screened to optimize the detection and DMF was used as a 37, and chemical reactions are described in Table 38. solvent. Three different polyrotaxanes varying by polymer Many glycosidases are able to catalyze transglycosylation nature, that is, poly(ethylene oxide) or polydimethylsiloxane reactions that are useful in synthesis. Some are listed in Table 31. and with a-org-cyclodextrins were evaluated. The 1,1,3,3- Zakariassen et al. (2011) have shown that the transglycosylation tetramethylguanidinium salts of both HABA and THAP properties of family 18 chitinases can be manipulated by mutations were found to be the most reliable and efficient matrices that affect the configuration of the catalytic machinery and the allowing poly[17]- and poly[18]rotaxanes with masses of affinity for sugar acceptors. It was proposed that the hyper- 24,804 and 26,447, respectively, to be measured. transglycosylating mutant ChiA-D313N_F396W might find applications for such synthetic purposes. Endo D, an endo-b-N- B. Synthesis and Analysis of Carbohydrate–Protein acetylglucosaminidase from Streptococcus pneumoniae has found Conjugates use for remodelling the Fc domain of IgG (Fan et al., 2012). MALDI has aided a study that has shown that synthesis of Work in this area is mainly directed toward vaccine production O-linked glycopeptides frequently result in substantial amounts and is listed in Table 40. Jahouh et al. (2012) have used MALDI- (up to 80%) of epimerization at the a-position. Epimerization TOF and LC-MS to determine the glycation sites in a synthetic was shown to be due to a combination of factors such as an lactose-BSA conjugate vaccine in which the lactose was linked energetic preference for the unnatural epimer over the natural via squaric acid chemistry. Analysis of tryptic and GluC V8 epimer and the rate of peptide coupling. It was also shown that digests identified 15 glycation sites where the hapten:BSA ratio use of 2,4,6-trimethylpyridine as the base in peptide couplings was 5.1:1 but 30 sites when the ratio was 19:1. Glycation, at produces glycopeptides with high efficiency and low epimeriza- lysine residues, appeared to be mainly on the surface of the BSA tion (Zhang et al., 2012l). carrier.

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HO HO HO HO HO HO HO HO HO OH OH O O HO OH OH HO O OH HO O HO OH O HO O OH O O OH OH

NH NH O O NH O O OH O O NH O NH O HO O O O OH O HO O O O NH HO O O O OH OH O O O OH H O HO OH N O O O O O O O HO O O OH HO O O OHOH H O O N O O O OH N N NH N N O O N O O O O N OH N O O N N N NH N O O N

O O O OH O O HO O O NH O O O HO OO O O HO O O N O N N O O N N O O O N OHOH HO H O O O O N O O HO OH O O O N O O H HO O OH HO N O O N N O O O N N O N O O OHOH O O O O O N O O H O O O OH O OH O O O

N O N NH O N N N O O N N O O HO O O O N N N NH O N N O O N O HO O O H HO O OH HO O OH O O HO O O O O O O O HO N OH O H O O HO O HO HO OH O O O O HN O O OH HO O O O O OH O HN O NH O O O HO O HN HN O O HN

O HO HO O HO O OH O O HO OH O OH HO HO OH OH O O HO HO HO OH OH OH OH OH OH OH OH OH

108

(NaO3S)O O O

O O O n1 CH3 CH3

(CH3)3Si n2

109

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TABLE 34. Use of MALDI analysis to monitor glycosylation in biopharmaceuticals and related materials Expression Biopharmaceutical Methodsa Notes Reference system Peptide tag with N-glycosylation HEK293 or CHO PNGase F, TOF, (Kaup et al., A1AT site attached to protein to increase cells N-glycans (per-Me) 2011) glycosylation 3D5 scFv TOF/TOF (DHB), Quantitative production of (Lizak et al., Antibody Escherichia coli glycopeptides (per- glycosylated protein. Glycans with 2011) fragment Me) bacillosamine, GalNAc and Glc. Afucosylated Lemna aquatic Fucose and xylose eliminated by TOF, glycans (2- (Gasdaska et Rituximab plant-based genetic engineering. Truncated AA) al., 2012) (BLX-300) system biantennary glycan PNGase F, TOF N-glycan identification (bi-, tri-, Alpha-1- Human neuronal (Blanchard et (arabinosazone), N- tetra-antennary complex) and antitrypsin cell line al., 2011b) glycans (per-Me) biological activity PNGase F, TOF Method development, acidic (Salinas et al., Agalsidase alfa Commercial (DHB), N-glycans glycans, high-mannose, hybrid, 2012) (per-Me), ESI complex, sialylated. PNGase F, Addition of polysialic acid chains Antibody TOF/TOF (DHB), (Chen et al., HEK cells to biantennary glycans to modify fragments N-glycans (Per- 2012a) half-life Me) Anti-HER2/neu Development of a method to purify (Jiang, et al., Pichia pastoris TOF, glycans receptor IgG1 the product. 2011b) Plants lacking α1,3FucT and XylT Endogenous Arabidopsis shown to produce triantennary (Nagels et al., TOF glycans thaliana glycans after incorporation of 2012) GnT-IV TOF/TOF (2,4- Assay in human Development of methods for (Fania, et al., Erythropoietin DHP, CHCA), serum clinical monitoring of EPO 2011) glycoproteins Expression of β-1,4-Gal- PNGase F, R-TOF Drosophila S2 β (Kim et al., Erythropoietin (DHB), N-glycans transferase and suppression of -N- cells 2011b) (2-AB) GlcNAc-ase to aid synthesis of complex N-glycans Peptide tag with N-glycosylation HEK293 or CHO PNGase F, TOF, (Kaup, et al., Erythropoietin site attached to protein to increase cells N-glycans (per-Me) 2011) glycosylation PNGase F, Comparison with methods such as 15 Recombinant TOF/TOF (DHB), HPLC and HPAEC for (Yuen et al., Erythropoietin preparations N-glycans (free and determination of Z-number (total 2011) 4-AA) negatively charged N-glycans) (Nett et al., Erythropoietin Pichia pastoris TOF Optimization of production 2012) Development of glycopeptide PNGase F, L-, R- enrichment method with amine- TOF/TOF (CHCA, (Kuo, et al., Erythropoietin BHK21 cells functionalized nanoparticles, DHB), glycans 2012a) sialylated bi-, tri-, tetra-antennary (per-Me) complex Glycoengineering the N-acyl side PNGase F, TOF (s- Human in CHO chain of sialic acid of human (Werner et al., Erythropoietin DHB), N-glycans cells erythropoietin shown to affect its 2012) (per-Me) resistance to sialidase Production of asialo-erythropoietin Physcomitrella (Parsons et al., Erythropoietin TOF devoid of Lewis A and other plant- patens (moss) 2012) typical carbohydrate determinants Enhancement of EPO production and glycosylation in serum-free Human in CHO PNGase F, R-TOF, (Park et al., Erythropoietin suspension culture of CHO cells cells N-glycans (per-Me) 2012d) through expression and supplementation of 30Kc19 Assessment of quality and From PNGase F, R-TOF structural integrity of a complex Follitropin (Liu, et al., commercial (ATT, 2,6- glycoprotein mixture following alpha 2011a) Gonal-F DHB/spermine) extraction from the formulated drug product

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TABLE 34. (Continued) Human in Trypsin, PNGase A Modified by encoding for HIV anti-gp41 modified (in gel) R- Caenorhabditis elegans GlcNAc- (Palmberger et antibody 3D6 baculoviral TOF/TOF (ATT), transferase II and bovine β1,4-Gal- al., 2012) insect cells N-glycans transferase I. Called SweetBac PNGase F, TOF Method development, acidic (Salinas, et al., Idursulfase Commercial (DHB), N-glycans glycans, sulfated biantennary 2012) (per-Me), ESI complex glycan Enhancement of sialylation on PNGase F, TOF, humanized IgG-like bispecific (Onitsuka et IgG CHO Cells N-glycans (2-AP), antibody by overexpression of al., 2012) LC-MS/MS α2,6-sialyltransferase Production, characterization and PNGase F, TOF, (Yu et al., IgG CHO Cells pharmacokinetics of antibidies ESI 2012b) carrying Man5GlcNAc2 Trypsin, PNGase Use of tricistronic vectors for F, TOF/TOF enhancing generation of high (Ho et al., IgG CHO Cells (DHB), N-glycans monoclonal antibody expressing 2012) (per-Me) CHO cell lines IgG (four CHO Cells and PNGase F, Use of multivariate statistics to (Thuy et al., therapeutic mouse myeloma TOF/TOF (DHB), differentiate antibodies based on 2012) antibodies) cell line N-glycans glycosylation PNGase F, TOF IgG Chemoenzymic Use of endo S to transfer sialylated (Huang et al., (DHB, THAP), N- (Rituximab) glycoengineering biantennary glycans to Fc region 2012b) glycans (2-AB) PNGase F, TOF Structural determination (high- IgG (Montesino, et Commercial (DHB), N-glycans, mannose, hybrid, biantennary (Nimotuzumab) al., 2012) HPLC (2-AB) complex) PNGase F Development of high-throughput (automated system) method for N-glycan profiling (Thuy, et al., IgG1 Human R-TOF based on a microfluidic CD 2011) (DHB/DMA), N- platform and MALDI-MS (see glycans text) Optimization of a glycoengineered PNGase F, TOF, (Ye et al., IgG1 Pichia pastoris cultivation process for commercial N-glycans (2-AB 2011) antibody production Isoforms in different batches traced MALDI and LC- (Sundaram et IgG1 - to sialic acid content and MS/MS al., 2011) truncation of C-terminal lysine Humanized P. pastoris shown to (Cukan et al., IgG1 Pichia pastoris TOF produce glycoproteins that do not 2012) bind to DC-SIGN PNGase F, IgG1 AGE1.CR.pIX TOF/TOF Practical details targeted at (Ogorek et al., avian cell line (arabinosazone), N- fucosylation machinery 2012) glycans IgGs produced in CHO cells PNGase F, TOF contain less galactose on (Raju & IgG1 Various cell lines (DHB), N-glycans biantennary glycans than those Jordan, 2012) from mouse myeloma cell lines IgG fused to the Hydrazine, TOF Presence of sorting signal leads to vacuolar sorting Tobacco BY2 (Misaki et al., (DHB), glycans (2- increased production of signal of cells 2011) AP) Man Fuc Xyl GlcNAc sporamin 3 1 1 2 Spodoptera frugiperda Sf9, IgG1 (human Trichoplusia ni Development of glycoengineered R-TOF/TOF (Palmberger et anti-gp41 “High Five”, and insect cells as alternative to CHO (DHB) al., 2011) antibody 3D6 S. frugiperda cells for antibody production SfSWT-1 and CHO cells Ectopic expression of human (Dreesen & IgG PNGase F, TOF protein mTOR shown to increase CHO-K1 Fussenegger, (Rituximab) (DHB) viability, robustness, proliferation, 2011) and antibody production

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TABLE 34. (Continued) Anti-galactose-α-1,3-galactose IgE from allergic patients shown not to (van Bueren et IgE Human serum PNGase F, TOF bind α-galactosylated glycans on al., 2011) intact therapeutic antibodies Various (CHO, PNGase F, TOF, Study of N-glycosylation of IgY (Kondo et al., IgY chicken N-glycans (2-AP) expressed in different systems 2012) hybridoma, etc.) MALDI-TOF to estimate N-glycan Interleukin-3 (Li et al., Pichia pastoris TOF, protein mass after PNGase F (human) 2011b) deglycosylation Use of combinatorial genetic K3 Domain PNGase F, TOF (s- (Nett et al., Pichia pastoris library approach to engineer reporter protein DHB), N-glycans 2011) human-type glycosylation Structural characterization of the PNGase F, L-, R- Milk of site-specific N-glycosylation of TOF/TOF (DHB), (Yu et al., Lactoferrin transgenic wild-type and recombinant human N-glycans (per- 2011d) cloned cattle lactoferrin (high-mannose, bi-, Me), GC/MS triantennary complex) PNGase A, Characterization of the single- MBP10 Arabidopsis alg3 (Henquet et TOF/TOF (DHB), chain Fv-Fc antibody, mainly antibody mutant seeds al., 2011) N-glycans Man5GlcNAc2, Monoclonal QIT-TOF (DHB), Methods for detection of α-Gal (Maeda, et al., Commercial antibodies (six) glycans (2-AA) and Neu5Gc. 2012) Human in FUt8 Non- Glycans without fucose. Did not (Moldt et al., knockout CHO TOF fucosylated b12 improve protection against HIV 2012) cells Plantibodies Pepsin, PNGase A, Differential N-glycosylation of a CB.Hep1(- and TOF, glycans (2- monoclonal antibody expressed in (Triguero et +) KDEL and Tobacco leaves AB), tobacco leaves with and without al., 2011) CB.Hep1 from exoglycosidase, endoplasmic reticulum retention mouse ascites HPLC signal PNGase F, pronase, TOF Comparison of methods and (Schiel et al., Rituximab Commercial (DHB), N-glycans, identification of desirable 2012) glycoproteins, reference material characteristics LC/MS PNGase F, TOF Method development, acidic Velaglucerase (Salinas, et al., Commercial (DHB), N-glycans glycans, high-mannose with alfa 2012) (per-Me), ESI mannose phosphate PNGase F, TOF, Engineered to produce human (Hu et al., Insect cells Cells N-glycans glycosylation 2012) aFormat (not all items present): Glycan release method and/or protease, MALDI method (matrix), compounds run (derivative), other methods.

XXIII. MISCELLANEOUS STUDIES XXIV. CONCLUSIONS

The uses of MALDI in miscellaneous biochemical reactions MALDI continues to be a major technique for carbohydrate are listed in Table 41. Release of rhodamine B from galactose- analysis. It gives a cleaner proﬁle of glycan mixtures than capped mesoporous silica nanoparticles in the presence of electrospray ionization because of the absence of multiple b-galactosidase has been used as a model for testing drug- charging and signiﬁcant in-source fragmentation. Although targeting systems. Released galactose was monitored by the ion source conditions in electrospray instruments can be MALDI-TOF MS (Agostini et al., 2012). optimized to virtually eliminate fragmentation, multiple charg-

TABLE 35. Reviews and general articles containing applications of MALDI to carbohydrate synthesis Subject Citations Reference Large-ring cyclodextrins 91 (Endo, 2011) Precision polysaccharide synthesis catalyzed by enzymes 319 (Kadokawa, 2011) Chemical methods for degradation of target oligosaccharides using designed (Takahashi & 56 light-activatable organic molecules. Summary mainly of authors’ work Toshima, 2012b) (Sebestik et al., Peptide and glycopeptide dendrimers 608 2011) Chemical and enzymatic chondroitin sulfate synthesis 24 (Vibert et al., 2011) Photoaffinity probes for studying carbohydrate biology 55 (Yu et al., 2012c)

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TABLE 36. Use of MALDI MS for monitoring products of synthetic reactions Carbohydrate Methodsa Synthetic methods and comments Reference Monosaccharides 5-O-alkyl-1,4-imino-1,4- R-TOF Synthesis and anti-cancer activity (Bello et al., 2011) dideoxyribitols Branched tetrahydrofurane - R-TOF Synthesised from pyrolysis product of (Defant et al., 2011) sugar amino acid (DHB) cellulose on the gram scale As a second-generation iminosugar-based 1 C Butyl-1,4-dideoxy- TOF/TOF (oral glucosidase inhibitor for (Kato et al., 2012 ֿ ֿֿ ֿ (1,4-imino L arabinitol (DHB improving postprandial hyperglycemia ֿֿ 1-Deoxy-D-galacto- As -galactosidase inhibitors and nojirimycins with dansyl TOF potential probes for GM1 gangliosidosis capped N-substituents affected cell lines D-Galactofuranosyl New, non-thermodynamic approach to the TOF (DHB) (Vojtech et al., 2011) nitromethanes synthesis N-Glycooxazolines, N- glycoaminooxazolines, and TOF One-pot synthesis from glycals (Reid et al., 2012) N-glycothiazolines Synthesis by stereospecific ring-opening -Glycosyl thiols MALDI (Zhu et al., 2011) of 1,6-anhydrosugars Me- (7,8-di-O-benzoyl-4,5-O- isopropylidene-3-deoxy-D-manno-2-oct- (Ichiyanagi et al., Kdo Derivative TOF ulopyranoside)onate for synthesis of inner 2011) core of LPS Attached groups were RS-, R(SO)- -D-Mannose with anomeric MALDI et al., R(SO )-. R=Long-chain alkyl or sulphur-containing groups (DHB) 2 2011b) cyclohexyl Me-4-O-Bz-2,3-di-O-Me-6- (Matwiejuk & Thiem, TOF For study of hydroxy-group acidities O-tri-PhMe- -D-Galp 2012) Monosaccharide-guanidine TOF For mitochondrial targeting (Lee et al., 2011g) conjugates Monosaccharide-2-ethyl-2- TOF/TOF To investigate ring-opening (Miao et al., 2011) oxazoline conjugates (DCTB) polymerization Sialic acid C-glycosides with R-TOF, By cross metathesis to obtain ligands for (Meinke et al., 2011) aromatic residues FAB, ESI Trypanosoma cruzi trans-sialidase Sulfoquinovose (6-deoxy-6- Annual bio-production = 1010 tons. TOF (Denger et al., 2012) sulfoglucose) Shown to be degraded by several bacteria Oligosaccharides Use of 2,2,2-trichloro-ethoxy carbonyl N-acetyl glucosamine (Enugala & Marques, TOF (Troc) as an amino- and 3-OH- protecting disaccharide with free 3-OH 2012) group N-Acylated-low molecular Acylated with N-OH-tetradecanoic acid. (Naberezhnykh et al., TOF weight chitosan For preparation of coated liposomes 2011) Self-assembling properties with octyl, (Kanemaru et al., 6-O-Alkyltrehaloses TOF (DHB) decyl, dodecyl, tetradecyl, and hexadecyl 2012) chains under aqueous conditions 2-Aminoethyl glucosamine sulfoform MALDI Solid-phase synthesis (Liu & Wei, 2012) intermediate C-Arabinofuranosides TOF Stereospecific synthesis (Patil et al., 2012) Azido-functionalized cyclic Investigation of the compatibility of phosphate-linked TOF (DHB) azides in phosphoramidite-based (Coppola et al., 2011) oligosaccharide analogue couplings Bi-fluorescently-labelled As substrates for -amylase on the basis TOF (FAB) (Oka et al., 2012) maltooligosaccharides of fluorescence resonance energy transfer Blockwise alkylated (1 4) R-TOF As surfactants. Influence of configuration (Nakagawa et al., linked trisaccharides (DHB) of anomeric position 2011a) Symmetrical nitrogen containing ring Carbohydrate-based TOF (Rathjens & Thiem, structures with two or four glucose units azamacrocycles (CHCA) 2011) by Richman Atkins cyclisation Synthesis by lysozyme-mediated -Chitin-like substance TOF (Hattori et al., 2012b) transglycosylation One-pot chemoenzymatic synthesis via specific transglycosylation of Chitoheptaose TOF (Yoshida et al., 2012) chitopentaose-oxazoline on a chitinase- template

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TABLE 36. (Continued) By enzymatic hydrolysis of chitosan for Chitooligosaccharides TOF (Wu et al., 2012) study of inhibition of angiogenesis Enzymatic hydrolysis of chitosan. Anti- ( imùnek et al., Chitooligosaccharides TOF microbial action on human colonic 2012) bacteria Synthesis by a hypertransglycosylating Chitooligosaccharides (long- TOF/TOF (Purushotham & processive endochitinase of Serratia chain) (DHB) Podile, 2012) proteamaculans 568 By depolymerization chitosan by (Tishchenko et al., Chitosans TOF (DHB) enzymatic hydrolysis, oxidative reaction 2011) or microwave irradiation. Chitosan oligosaccharides Effects of molecular weight and degree of TOF (Park et al., 2011b) from enzymatic hydrolysis deacetylation on antitumor activity (Prasertsung et al., Chitosan oligosaccharides TOF Synthesis with a solution plasma system 2012) Effects on activation of murine spleen Chitosan oligosaccharidesTOF CD11c+ dendritic cells via toll-like (Dang et al., 2011) receptor 4 Cyclic phosphate-linked As saccharide-based synthetic ion (Mangiapia et al., TOF oligosaccharides transporters 2011) One-pot synthesis of cycloamyloses from Cycloamyloses TOF (DHB) sucrose by combined reaction of (Kim et al., 2011a) amylosucrase and 4- -glucanotransferase Used to show that some glycosyl donors Cyclopropyl analogues of MALDI, (Kumar & Whitfield, form oxacarbenium ions in glycosylation mono- and disaccharides ESI 2012) reactions but more reactive donors do not -Cyclosophoro- As chiral additives in capillary (Kwon & Jung, octadecaoses -succinyl TOF (DHB) electrophoresis of flavanones 2011b) substituted Chiral separation of catechin by capillary -Cyclosophoro- electrophoresis with - octadecaoses -acetyl or TOF (DHB) cyclosophorooctadecaose isolated from (Kwon et al., 2011a) succinyl substituted Rhodobacter sphaeroides as chiral selectors Di-carba analogues of MALDI Use of intramolecular N-glycosylation (Duchek et al., 2011) guanofosfocins For development of multivalent Disaccharide with mannose TOF nanomaterial for study of carbohydrate (Wang, 2012) unit and thiol tether interactions Disialic acid-embedded Use of 1,5-lactamized sialyl-Glc acceptor TOF (Shimizu et al., 2011) glycan of ganglioside HPG-1 and 8-O-Lev-N-Troc-sialic acid donor Drosocin and derivs. linked Synthesis, functional and structural TOF (Ahn et al., 2011a) O-GalNAc at Thr11 residue characterization Epoxidized fatty acid esters TOF (Pan et al., 2011b) of sucrose (CHCA) conditions Fluoro-sugar-terminated For investigating sequence specificity of TOF (Brown et al., 2012a) oligosaccharides carbohydrate polymerase R-TOF From lactose or skim milk using the - (Rodriguez-Colinas Galacto-oligosaccharides (DHB + galactosidase from Bacillus circulans et al., 2012) NaI) TOF/TOF For characterization of -1,4-galactan - (2-OH- (Liwanag et al., -D-(1 4)-Galactopentaose 1,4-galactosyltransferase in Arabidopsis benzoic 2012) thaliana acid) Fluorescence-labeled hexasaccharide as a -Glc(1 2) -Glc(1 3) - substrate for the processing enzyme - Glc(1 3) -Man(1 2) - TOF (DHB) (Iino et al., 2012) glucosidase I. Facile synthesis of 1,2-cis Man(1 2) -Man glucosidic linkage Glycosaminoglycan Use of a glucuronate glycosyl donor with (Furukawa et al., TOF disaccharides a 2-O-acyl-6,3-lactone structure 2011b) Synthesis from N-glycosyl (Gaitonde & -Glycosyl amides TOF dinitrobenzenesulfonamides Sucheck, 2012) -glycosyl disulfides MALDI Glycosyl disulfides prepared in a few hours from per-O-Ac (Adinolfi et al., 2011) (DHB) precursors Elaboration to disarmed-armed iterative -Glycosyl imidinium triflate TOF (Lin et al., 2012c) glycosylation Synthesis by Pasteurella multocida (Chavaroche et al., Heparosan oligosaccharides TOF (DHB) PmHS2 single-action transferases 2012)

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TABLE 36. (Continued) 1 ,2,3,3 ,4,4 ,6 -Hepta-O- Mild and economic protocols for the acetyl- 6-O-methacryloyl TOF selective derivatization of sucrose under (Barros et al., 2011) sucrose microwave irradiation 6-O-Hexadecyl and 6-O- Synthesis and self-assembling properties (Ohkawabata et al., TOF (DHB) octylsucroses under aqueous conditions 2012) HNK-1 epitope: 3-O-sulfo- - Prepared by enzymatic glucuronylation of TOF/TOF, D-GlcpA-(1 3)- -D-Galp- allyl lactoside by an engineered (Bastide et al., 2011) ESI (1 4)- -D-Glcp-allyl recombinant Escherichia coli strain R-TOF As new substrates for -N- Immunomodulatory (DHB, acetylhexosaminidase-catalyzed synthesis disaccharides 2011) CHCA) of immunomodulatory disaccharides For redesign of an isomaltulose synthase Isomelezitose TOF (DHB) to an isomelezitose synthase Potential use of oligosaccharides as Lactoside-based trisaccharide TOF unique bioorthogonal cross-linking (Fyrner et al., 2012b) and cholesterol conjugate (CHCA) derivatives Synthesis and hydrolysis by Dispersin B -(1 6)-linked D-GlcNAc TOF (hexosaminidase from Aggregatibacter (Fekete et al., 2011) substrates actinomycetemcomitans) Low-MW chitosan By chitosanase hydrolysis of chitosan. TOF (Chung et al., 2012a) oligosaccharides Anti-inflammatory effects Mannosides with (Obermajer et al., TOF Synthesis as DC-SIGN antagonists hydrophobic substituents 2011) 15N, 13C 2 8-sialic acid Evidence for helical structure in a TOF (Battistel et al., 2012) oligomers tetramer of 2 8 sialic acid Oligo( -D-glycosyl Use of a phosphoramidite method via TOF (Fujita et al., 2011b) phosphate) derivatives boranophosphate intermediates Orthogonally protected For synthesis of 6-sulfated derivatives MALDI (Liu et al., 2012g) disaccharide with terminal ethylamine Pustulooligosaccharides ( - Synthesis and incorporation into plant cell (1,6)-linked gluco- TOF (DHB) walls 2012) oligosaccharides) S-linked glycoconjugates and TOF Synthesis by thiol-ene coupling reaction

S-disaccharides (THAP) of enoses c and 6-O-sulfate Synthesis, four stages, chemical addition (Pazynina et al., TOF (DHB) (trisaccharides) of sialic acid (72% yield) 2012) Automated synthesis from novel sialyl - Sialylated oligosaccharides MALDI (Esposito et al., 2012) (2 3) and -(2 6) galactosyl imidates Sulfated Lewis A L-TOF Natural L-fucose moiety replaced by D- pentasaccharide - sulfonic (Jakab et al., 2012) (THAP) arabinose acid mimetic Synthesis of two different series of Sulfonic acid-containing (2 5)- -linked homologous keto- maltose-type keto- TOF oligosaccharides up to tri- and oligosaccharides tetrasaccharide Sulfonic acid mimetic of the Investigation of glycosylating properties TOF sialyl Lewis X of 1-deoxy-1-ethoxysulfonylhept-2- (THAP) tetrasaccharide ulopyranosyl derivatives For production of functionalized carbon Thiomannosyl dimer TOF (Zhang et al., 2011j) nanotubes Mimic selected branches of gp120 TOF -Navas et Tri- and tetra-mannosides glycans. For binding studies to antibody (THAP) al., 2012) 2G12 Synthesis by click chemistry. Evaluated 1,2,3-Triazolo-linked octyl Q-TOF in mycobacterial mannosyltransferase (1 6)- -D-oligomannosides (DHB) 2011a) assay N,N,N-Trimethyl-D- Synthesis as selective inhibitors of glucosamine-(1 4)- MALDI glycosyl hydrolase family 20 -N-acetyl- (Yang et al., 2011f) chitooligosaccharides D-hexosaminidases Synthesis of four bifunctionalized Tri-, penta-, and orthogonally N-protected heptasaccharides, with TOF oligosaccharides derived from lactose and (Fyrner et al., 2012a) orthogonally N-protected mannose, intended as cross-linking amino residues derivatives

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TABLE 36. (Continued) TOF/TOF By sulfation of xylan from different Xylan sulfates (Daus et al., 2011) (DHB) sources using SO3/pyridine or DMF Chemo-enzymatic synthesis of R-TOF Xylogluco-oligosaccharides compounds. with up to 20 residues and (Lopez et al., 2012) (DHB), ESI their interactions with cellulose Structure and synthesis of antifreeze TOF (DHB, Xylomannan xylomannan from Upis ceramboides (Ishiwata et al., 2011) ESI (Alaskan beetle) Polysaccharides From thermomechanical pulping of O-Acetyl- (Edlund & TOF spruce for synthesis of halide- galactoglucomannan Albertsson, 2011) functionalized polymerase initiators Non-reducing cellulose mimics prepared Alkyl -D-cellulosides TOF (DHB) from microcrystalline cellulose or (Meiland et al., 2011) cellulose triacetate By cellulolytic enzyme-mediated R-TOF transglycosylation in an aqueous medium Cellulose II-like substance (Hattori et al., 2012a) (DHB) with endoglucanase I from Hypocrea jecorina Diblock methylcellulose L-TOF Synthesis by via Huisgen 1,3-dipolar (Nakagawa et al., analogues (DHB) cycloaddition 2012) Methylcellulose glutarate MALDI For sustained drug release (Ali et al., 2011) N-linked glycans Biantennary N-glycans with Two approaches to synthesis - for use in (Hagiwara et al., LacNAc and LacdiNAc at the TOF (DHB) Fmoc solid-phase peptide synthesis 2011) nonreducing end Fucosylated biantennary For synthesis of the -subunit of the (Nagorny et al., TOF glycosylamine human follicle-stimulating hormone 2012) For first total chemical synthesis of the - Fucosylated biantennary (Aussedat et al., TOF subunit of human follicle-stimulating glycosylamine 2012) hormone -Mannose linkage created by C-2 Fully O-benzylated N-linked epimerization of initially introduced -D- core pentasaccharide glycosyl TOF (DHB) gluco-unit via DMSO/Ac O oxidation azide 2 followed by stereoselective reduction Poly-N-acetyllactosamine- For recognition studies by human and (Nycholat et al., TOF (DHB) extended biantennary avian influenza A virus hemagglutinins 2012) Sialylated biantennary Enzymatic synthesis. Analysed as TOF/TOF (Barb et al., 2012) glycans on IgG Fc permethylated, released glycans, O-linked glycans Gal 1 4Gal 1 3GalNAc shown to be the dominant epitope of the mucin-type EM2 O-glycans TOF (Yamano et al., 2012) glycoprotein (Em2) from Echinococcus multilocularis Poly-N-acetyllactosamine- For recognition studies by human and (Nycholat, et al., TOF (DHB) extended avian influenza A virus hemagglutinins 2012) Glycopeptides/Glycoproteins (Horowitz et al., Adenoassociated viral capsids TOF/TOF Decreased infectivity 2011) TOF (DHB, Threonine glycosidically linked to -D- Antifreeze glycopeptides (Nagel et al., 2011) s-DHB) Gal-(1 3)- -N-acetyl-D-GalN Influence of carbohydrate variations on Antifreeze glycopeptides TOF (DHB) (Nagel et al., 2012) antifreeze activity Antifreeze glycopeptides and From dodecapeptide with four Gal- (Wilkinson et al., TOF (DHB) glycoproteins GalNAc residues 2012b) Synthesis of C-linked triazole-containing Antifreeze glycopeptides and R-TOF (Capicciotti et al., analogues and their ability to inhibit ice glycoproteins (DHB) 2011) recrystallization Antifreeze glycoproteins Studies on the effect of the number of TOF (Ahn et al., 2012b) (homodimeric) sugar moieties on the antifreeze activity For targeting the RNA that causes (Childs-Disney et al., D-Arg -based glycopeptides TOF 9 myotonic dystrophy type 1 2012) Bi- and trivalent glycopeptide As inhibitors of type 1 fimbriae-mediated (Schierholt et al., TOF -D-mannopyranosides bacterial adhesion 2011) C-Linked antifreeze TOF Tetramer of tripeptide with Gal or (Gal) (Leclère et al., 2011) glycoprotein analogues 2

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TABLE 36. (Continued) Disaccharide-N[Me] -O- -Castells et GFKKG-amide TOF For studies of sugar-protein interactions al., 2012) glycopeptides Compounds prepared by substitution of the GalNAc- -O-Thr11 residue with O- Drosocin analogs TOF linked glyco-peptoid residues: Effect on (Ahn et al., 2011b) antibacterial activity and conformational change Cyclic antifreeze TOF Synthesis and evaluation of antifreeze (Ahn et al., 2012a) glycopeptide (CHCA) activity Galactose containing cell- R-TOF Synthesis, cellular uptake and biophysical penetrating peptides (CHCA) properties 2012) Chemoenzymatic synthesis. Presence of Glycoforms of antibody Fc TOF (DHB) bisecting glycan shown to enhance (Zou et al., 2011) domain. affinity of Fc to Fc IIIa receptor Use of cross metathesis assisted solid- Glycopeptoids TOF (Khan et al., 2012) phase synthesis To investigate class II MHC binding and CII259 273 glycopeptide (Andersson et al., TOF T-cell responses associated with library (from type II collagen) 2011) autoimmune arthritis Use of 2-deoxy-2-[18F]fluoroglucose to (Boutureira et al., [18F]-labelled glycoproteins TOF label at Cys or dehydro-Ala 2011) Fmoc-based chain elongation. O- to S- Glycopeptide aryl thioesters TOF (Zheng et al., 2011a) acyl shift. Alkyl thioester exchange Glycopeptide from HIV Practical details of an on-resin convergent (Chen & Tolbert, gp120 containing a high TOF synthesis 2011) mannose N-linked glycan Glycopeptides linked to TOF/TOF Synthesis aimed at a fully synthetic mono-, di-, and tetra-valent (CHCA, MUC1-based anticancer vaccine. Linkage (Cai et al., 2011a) lipopeptides DHB), ESI Glycopeptide with MUC1 For improved recognition of tumor- (Lakshminarayanan TOF epitope associated mucin MUC1 et al., 2012) MALDI Synthesis by hetero-Diels Alder addition C-Glycosylated amino acids (Massen et al., 2011) (DHB) of ethyl 2-nitrosoacrylate to exo-glycals TOF/TOF Glycosylated formaecin I and Changing the glycan moiety shown to (CHCA), (Talat et al., 2011) drosocin change antibacterial activity ESI O-Glycosylated lysine-N- For synthesis of O-glycopolypeptide TOF (DHB) (Pati et al., 2012b) carboxyanhydride monomers polymers Glycosylated MUC6 TOF, FT- Glycosylation with GalNAc transferases. (Freire et al., 2011) glycoprotein MS Shown to modulate immunogenicity For identification of potential gG-2 Glycopeptide library TOF immunodominant O-glycopeptide (from herpes simplex virus 2) epitopes on viral envelope glycoproteins To study the effect of mannosylation on Mannosylated glycopeptides TOF (Tran et al., 2012a) GalNAc addition in -dystroglycan MUC1 glycopeptide Synthesis by solid-phase synthesis and (Wilkinson et al., TOF, ESI thioesters ligation by direct aminolysis 2011) MUC1 glycopeptides TOF For generation of microarrays (Blixt et al., 2011) For construction of glycopeptide array for (Pedersen et al., MUC1 glycopeptides TOF (DHB) serum profiling of colon cancer patients 2011b) TOF/TOF Self-assembling, adjuvant-free MUC1 glycopeptide vaccine (DHC, (Huang et al., 2012d) glycopeptide for cancer therapy. CHCA) Study of the effect of O-glycosylation on MUC4 and MUC5AC TOF/TOF (Hashimoto et al., the conformation of synthetic mucin glycopeptides (DHB) 2011b) peptides Mucin fragments (MUC2, To study the binding of lectin domains of (Pedersen et al., MUC4, MUC5AC, MUC6, TOF (DHB) polypeptide GalNAc transferases 2011a) and MUC7 As model compounds for ETD studies on (Thaysen-Andersen Mucin glycopeptides TOF (DHB) densely glycosylated mucin-type peptides et al., 2011)

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TABLE 36. (Continued) (Barb & Prestegard, N-Glycans-IgG MALDI Remodelling of N-glycans on IgG, Fc 2011) Combined Fmoc/Boc strategy with N-Glycopeptides TOF , 2011) glycoamino acid building blocks To study effect of peptide chain on (Akasaka-Manya et O-Mannosyl peptides TOF activity of protein O-linked mannose al., 2011) 1 2-N-acetylglucosaminyltransferase 1 First total syntheses of glycopeptides TOF/TOF containing the tetrasaccharide O-Mannosyl peptides (S (THAP) Neu5Ac 2- 3Gal 1 4GlcNAc 1 2Man Perfluoroalkylated (Hoffmann- amphiphilic MUC1 TOF As tools for cancer immunotherapy al., 2011) glycopeptide antigens Phospho-glycopeptide TOF/TOF To examine protein glycosylation with (Mo et al., 2011) derived from -dystroglycan (DHB) emphasis on aberrant structures With 1,3-diol structure for glycopeptide (Tomabechi & Inazu, Pseudo glycoamino acid TOF synthesis 2011) Saposin C with complex-type TOF (DHB) Chemical synthesis (Hojo et al., 2012) glycans Synthesis by Fmoc-based solid-phase Sublancin (S-linked (Katayama et al., TOF peptide synthesis and chemoselective glycopeptide) 2011) disulfide formation reactions Use of mixed F Ph and o-FPh esters of Trisaccharide plus TOF 5 aliphatic dicarboxylic acids for peptide 2012), dodecapeptide derivative (CHCA) and protein conjugation Baltzer, 2012) Variable-number tandem repeat of tumor-associated FT-ICR Synthesis and immunological evaluation MUC1, universal T-cell (DHB, of self-assembling and self-adjuvanting (Wilkinson et al., helper peptide epitope THAP, tricomponent glycopeptide cancer- 2012a) PADRE and immunoadjuvant CHCA) vaccine candidates Pam3CysSer Xyloglucan-peptide R-TOF For the activation of cellulose surfaces conjugates (DHB) Carbohydrates from fungi Synthesis and demonstration that the S- and R-mannosylerythritol TOF (Fukuoka et al., diastereomers have different interfacial lipids (CHCA) 2012) properties and aqueous phase behavior Carbohydrates from algae 1,2-Diacyl-3-(N-acyl- - Q-TOF, FT- Eight acyl analogues via amino- -deoxy- -D- (Sun et al., 2012a) ICR (DHB) trichloroacetimidate donor glucosyl)-sn-glycerol Carbohydrates from protozoa, nematodes etc. Carbohydrate moieties Synthesis, antigenicity against human (Koizumi et al., from Toxocara larvae and TOF sera and structure-activity relationships 2012) their analogues Tetrasaccharide cap of the Synthesis by AuBr mediated selective 3 (Sureshkumar & Leishmania donovani TOF glycosylation of propargyl 1,2-orthoester Hotha, 2012) lipophosphoglycan in the presence of propargyl glycoside Tri-, tetra- and penta- Show good serodiagnostic potential to (Koizumi et al., saccharide from TOF detect infections caused by E. 2011) Echinococcus multilocularis multilocularis. Carbohydrates from plants Fragments of Synthesis of apiose-containing rhamnogalacturonan-II side (Nepogodiev et al., TOF oligosaccharide fragments of the plant chains A and B, and 2011) cell walls apiogalacturonan GPI Anchors Use of p-MeO-Bz group for permanent (Swarts & Guo, Clickable GPI anchors MALDI hydroxyl protection 2011) Fluorescently labelled GPI Borondipyrromethene (BODIPY) label to MALDI (Saikam et al., 2011) anchors study membrane interactions To study monosaccharide addition using a 7-Mer chondroitin with TOF flow-type 27 MHz quartz-crystal (Mori et al., 2012) GalNAc at non-reducing end microbalance First total synthesis of a GPI anchor GPI anchor of human TOF bearing a polyunsaturated arachidonoyl (Burgula et al., 2012) lymphocyte CD52 antigen fatty acid

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TABLE 36. (Continued) Synth. of Man- 1 6-Man- 1 4- S-glycosides of tri- to GlcNH2- 1 S-octyl, Man- 1 6-(Gal- penta-saccharide fragments 1 3)Man- 1 4-GlcNH - 1 S-octyl (Dettmann & Ziegler, TOF, FAB 2 related to the GPI anchor of and Man- 1 2-Man- 1 6-(Gal- 2011) Trypanosoma brucei 1 3)Man- 1 4-GlcNH2- 1 S-octyl, by a stepwise and block-wise approach Synthetic glycosides and related compounds Use of propargyl 1,2-orthoesters as Amino acid glycosides TOF (Shaikh et al., 2011) glycosyl donors Amino acid glycosyl For preparation of nanorods, micelles, TOF (Pati et al., 2012a) carbamates and organogels by click chemistry For treatment of genetic diseases caused (Kandasamy et al., Aminoglycosides TOF by nonsense mutations 2012) Amphiphilic disaccharide- Helical assembly of azobenzene- TOF conjugated carbohydrate with specific (Ogawa et al., 2012b) azobenzene conjugates affinity for lectins 2-Anthracenecarboxylates Diastereocontrolled (Fukuhara et al., tethered to cyclic TOF photocyclodimerization 2012) tetrasaccharides Synthesis from 5,10,15- Corrole-D-galactose tris(pentafluorophenyl) corrole and TOF (Cardote et al., 2012) conjugates 1,2:3,4-di-O-isopropylidene- -D- galactopyranose Synthesized by copper-mediated 1,3- dipolar cycloaddition reactions of (Nyuchev et al., Coumarin triazolylglycosides TOF carbohydrate azides and 4-alkynyl- 2011) substituted coumarins. Luminescence for surface imaging Decaprenylphosphoryl- As arabinofuranosyl donors with TOF (DHB) (Zhang et al., 2011d) arabinose analogues mycobacterial arabinosyltransferase 1,2-Diamino-4,5- Synthesis of a universal fluorescent methylenedioxybenzene- TOF (DHB) acceptor for HPLC analysis of pro- and (Keys et al., 2012) labeled trimer of 2,8-linked eukaryotic polysialyltransferases sialic acid Endohedral metallofullerene TOF Synthesis by carbine addition (Yamada et al., 2011) glycoconjugates Fluorous-tagged glycosides TOF Incorporation into cell membranes (Hatanaka, 2012) Synthesis and preliminary screening as (Mugunthan et al., O- -D-Galactopyranosides TOF/TOF potential mimic of UDP-Galp against 2012) Mycobacterium tuberculosis Galactose-appended For intracellular hepatocyte thiol imaging TOF (Lee et al., 2012f) naphthalimide in vivo Galactose-derived aryl Synthesis and screening against (Mugunthan et al., TOF enones Mycobacterium tuberculosis 2011c) Glyco-functionalized TOF (DHB), Functionalized with malonate for platinum complexes FAB complexation with Pt for cancer treatment 2012) Glycoporphyrins Q-TOF Synthesis and biological evaluation (Daly et al., 2012) Use of propargyl 1,2-orthoesters as Glycosyl carbamates TOF (Shaikh, et al., 2011) glycosyl donors TOF (2,4- As components of targeted delivery Lactose-PEG neoglycolipids DHB) systems of biologically active compounds Maltose-based gelators with TOF Click coupled to a maltose polar head by (Clemente et al., light-sensitive zobenzene (DCTB, a copper(I)-catalysed azide alkyne [3 + 2012a) units DHB) 2] cycloaddition Mannosidic squaric acid TOF (DHB, As ligands to inhibit bacterial adhesion to (Grabosch et al., derivatives CHCA) mannosidic surfaces 2011) Quaternary ammonium salt- TOF (Dmochowska et al., Synthesis and mutagenicity properties containing monosaccharides (CHCA) 2011) As fouling-resistant SAMs: Synthesis, Saccharide-functionalized TOF monolayer properties, and antifouling (Fyrner et al., 2011) alkanethiols (CHCA) behavior Synthesis from sucrose and vinyl laurate Sucrose monolaurate TOF by action of alkaline protease from (Wang et al., 2012h) Bacillus licheniformis

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TABLE 36. (Continued) 2-(2-(2-Thioethoxy)- ethoxy)ethoxy- -D- MALDI For construction of nanoparticles (Laurino et al., 2011) galactopyranoside 3-Thioglycosylated 5,6- Thioglycosylation using a selenium-based TOF (Adinolfi et al., 2012) diacetoxyindole derivatives dynamic-mixture method Glycolipids Arabinofuranoside-containing Synthesis and interaction with surfactant TOF (Naresh et al., 2011) glycolipids protein A Synthesis and binding to surfactant Arabinofuranoside-containing TOF protein A and effect on sliding motilities (Naresh et al., 2012) glycolipids of M. smegmatis Cholesteryl-6-O- tetradecanoyl- -D- MALDI Chemoenzymatic synthesis (Davis et al., 2012) glucopyranoside 4-O- -di-O-Ac- -di-O- Use for molecular dynamics simulations TOF, (Horikoshi et al., alkanoyl- -dmanno- of hydrophobic 1,2,4-trichlorobenzene on GC/MS 2011) pyranosyl)-D-erythritol hydrophilic TiO2 Condensation of protected glucose-6- Glucose monomycolate TOF tosylate with mycolic acids from M. (Prandi, 2012) tuberculosis Synthesized from 3,4,6-tri-O-acetyl-2- Lipid II phosphonate R-TOF acetamido-2-deoxy-1-thio- -D- analogues (THAP) 2011) glucopyranose 64Cu Liposomes from For imaging of tumor associated dipalmitoylphosphatidyl- TOF macrophages by positron emission (Locke et al., 2012) ethanolamine plus tomography mannotriose Long-chain amphiphilic Click chemistry. Effect of disaccharide (Clemente et al., TOF glycolipids polar head on hydrogel properties 2012b) Methyl ursolate 3-O- - Synthesis and biological evaluation as MALDI (Ren et al., 2012b) chacotrioside analogues H5N1 viral entry inhibitors TOF With alkyl chains at C . Antibacterial Oligorhamnoside derivatives 1 (Ding et al., 2011) (CHCA) properties Self-assembling glycolipids TOF By use of recombinant -glucosidase (Konishi et al., 2011) from ricinoleic acid (CHCA) from Geobacillus sp. Amphiphiles for solubilization and Steroids plus di-maltose TOF (Chae et al., 2012) stabilization of membrane proteins Sugar acrylate/acrylamide TOF Use of gold-catalysed glycosidations (Thadke et al., 2011) hybrids Synthesised by conjugating - -Tocopherol oligochitosan TOF tocopherolsuccinate to water soluble (Noh et al., 2011) conjugates oligochitosans. For siRNA delivery Cyclodextrins Fluorescent -cyclodextrin synthesized Anthracene appended - TOF/TOF by coupling an anthracene moiety via (Mallard et al., 2011) cyclodextrins (DHB) click chemistry. Asymmetric -CD-based star copolymer covalently For synthesis of multifunctional pH- TOF (Liu et al., 2012h) conjugated with doxorubicin disintegrable micellar nanoparticles and DOTA-Gd moieties TOF Structural and spectroscopic features of (Stancanelli et al., Butanoyl- -cyclodextrin (CHCA) lutein/butanoyl- -CD nanoassemblies 2012) Calix[4]arene- -cyclodextrin TOF Synthesis and adsorption to basic fuchsin (Wei et al., 2012a) Schiff base Cholesteryl-cyclodextrin TOF Synthesis and amphiphilic behavior (Bauer et al., 2011) conjugates (dithranol) 2 2 -Cyclodextrin dimers TOF (DHB, A cyclodextrin-based ratiometric sensor (Martos-Maldonado linked with fluorescent rigid FAB, ESI for bile salts et al., 2012) spacer arms DCC condensation between 3-manomino- - and - cyclodextrin with (Fujiwara & TOF 3-monodeoxy- cyclodextrin and benzoic phenylalkylamides acid, phenylpropionic acid and Takahashi, 2011) phenylbutylic acid -, -, and - cyclodextrins Used as building blocks for colloidal (Choisnard et al., bioesterified with decanoate TOF (DHB) nanoparticles 2011) chains

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TABLE 36. (Continued) -Cyclodextrin containing (Brandhuber et al., TOF/TOF Synthesis and use to detoxify tabun oxime groups 2012) [(6- - Cyclodextrin)- TOF Polymerization and hierarchical super- (Maeda et al., 2011) oxyphenyl]acetylene (CHCA) structured helix formation For functionalization of polysulfone - Cyclodextrin fatty acid TOF (DHB) hollow fiber membranes for plasticizer (Choi et al., 2012c) esters removal - Cyclodextrin-6- C- Synthesis in 10 steps. As artificial TOF aldehydes enzymes 2012) -, and -CDs bioesterified As artemisinin nanocarriers. Synthesis MALDI with decanoate chains and antimalarial assessment 2012) - Cyclodextrin with -NH- CO-O-C2H4-O-CO-C3H5 TOF For synthesis of polymer (Yan et al., 2011) chain Cyclodextrin-based Use of disulfide bonds at all primary OH TOF (DHP) (Wang et al., 2011a) nanotubes groups to link - cyclodextrin s Synthesis by controlled ring-opening Cyclodextrin-centered TOF (Normand et al., polymerization of cyclic esters from - polyesters (CHCA) 2012) cyclodextrin-diol (Takashima et al., Cyclodextrin dimers TOF For preparation of hydrogels 2012) Cyclodextrin dimers with TOF As supramolecular dioxygen receptors (Kano et al., 2012) porphinatoiron(II) (CHCA) Cyclodextrin-scaffolded Alamethicin = peptide. Conjugated via TOF alamethicin click chemistry as antibiotic 2012) Cyclodextrins with Synthesised by oxidation of carboxylic acids at the TOF corresponding allyl-substituted (Zhou et al., 2012d) secondary rim cyclodextrins Bis- -cyclodextrinyl- (Dumarcay- Contains long-chain aliphatic compounds diazacrown- TOF Charbonnier & threaded through cyclodextrin rings [2]cryptorotaxanes Marsura, 2012) Synthesis of an N-heterocyclic carbene -Cyclodextrin-imidazolium ligand and characterization of TOF (Legrand et al., 2011) salt organometallic complexes and Suzuki coupling -Cyclodextrin attached to TOF Synthesis and photophysical properties - (Cacciarini et al., green flurescent protein (dithranol, formation of self-inclusion complex 2012) chromophore DHB) -CD derivative containing As scavengers for neurotoxic (Zengerle et al., TOF/TOF an oxime-derived substituent organophosphonates 2011) TOF Linked through their secondary faces with (Casas-Solvas et al., -Cyclodextrin dimers (CHCA) rigid spacer arms, as hosts for bile salts 2011) -Cyclodextrin -pyromellitic (Krishnan et al., TOF (DHB) Study of complexation diimide complexes 2012) Prepared by click chemistry. Used for (Christensen et al., Cyclodextrin trimers TOF (DHB) recognition of peptides 2011) Cyclodextrin -based insulated Head-to-tail synthesis with per- TOF (Terao et al., 2011) molecular wire methylated cyclodextrin Click chemistry. CuI-catalyzed azide- Chiral amino acids linked to TOF/TOF alkyne cycloaddition from mono-6-azido- (Tran et al., 2011) two -CDs (DHB) -cyclodextrin With -Fuc-GlcNAc and -Fuc- - (Nakagawa et al., Cyclomaltoheptaose derivs TOF (DHB) GlcNAc substituents 2011d) 6-Deoxyacrylamido- - and - Discriminate between 1-naphthyl- and 2- TOF (Zheng et al., 2011b) -cyclodextrins naphthyl-methyl moieties To investigate interaction between -CD 6-Deoxy-6-amino- - and psychotropic drugs by surface (Kobayashi et al., TOF cyclodextrin 2011a) system 2-Functionalised PEGylated Use of click chemistry to modify MALDI and cationic -cyclodextrins secondary 2-OH group 2012) Glycol chitosan-graft- Evaluation as potential pH-sensitive carboxymethyl - TOF (Tan et al., 2012) anticancer drug carrier cyclodextrin

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TABLE 36. (Continued) Guanidino-substituted - - For siRNA delivery to prostate tumours MALDI (Guo et al., 2012a) cyclodextrins in mice Hetero-functionalized TOF Synthesis of artiicial glycosidases and (Petrillo et al., 2011) cyclodextrins (CHCA) phosphorylases Heptakis(2-O-sulfo-3-O- R-TOF Synthesis, and characterization of a new, methyl-6-O-acetyl)- - (THAP), single-isomer chiral resolving agent for (Tutu & Vigh, 2011) cyclodextrin ESI capillary electrophoresis His- -cyclodextrin and Lys- For combining with DNA to form (Bennevault-Celton TOF/TOF -cyclodextrin CDplexes et al., 2011) 6-Hydroxymethyltriazolyl-6- TOF Synthesis. Highly water soluble and structurally well-defined -cyclodextrin (Kim et al., 2012c) deoxy- -cyclodextrin (CHCA) click cluster For study of thermodynamics of 2-O-Me and 2-OH-propyl- - TOF complexation of tauro- and glyco- (Holm et al., 2011) cyclodextrin (CHCA) conjugated bile salts TOF Influence of degree and pattern of (CHCA/ substitution on the thermodynamics of Methylated -cyclodextrins nitro- complexation with tauro- and glyco- 2011) cellulose conjugated bile salts Mono 6-NH - -cyclodextrin 2 (Hocquelet et al., dimers bridged by N,N- TOF (DHB) Synthesis and inclusion properties 2011) succinyldiamide linkers Fluorescent derivative to study Mono-4-(N-6-deoxy-6- permeation and cellular distribution of amino- -cyclodextrin)-7- TOF (Wei et al., 2011) cyclodextrin by confocal laser nitrobenzofuran microscopy Mono-6-deoxy-6-azido- - TOF (DIT, Intermediate for synthesis of star polymer (Ren et al., 2011) cyclodextrin DCTB) library Mono-6-deoxy-benzimide- - As a chiral stationary phase in high- TOF (Li et al., 2011e) cyclodextrin performance liquid chromatography Mono-6-deoxy-(2,4- As a chiral stationary phase in high- TOF (Li et al., 2011d) dihydroxybenzimide)- -CD performance liquid chromatography TOF Mono-6-deoxy-6-ethylene- For synthesis of hybrid magnetic (CHCA), (Kang et al., 2011c) diamine- -cyclodextrin nanoparticles GC/MS Mono-[6-deoxy-6-(1- TOF To form supramolecular polymer (Zhang et al., 2012h) piperazinyl)]- -cyclodextrin Development of protein-cage-based Mono-6-(p-toluenesulfonyl)- delivery nanoplatforms by polyvalently TOF (DHB) (Kwon et al., 2012a) 6-deoxy- -cyclodextrin displaying -cyclodextrin on the surface of ferritins New solid support to get a variety of C-6 Monosubstituted cyclodextrin monofunctionalized CDs ( , , Me CD (Di Fabio et al., TOF derivatives and HP CD) covalently linked through a 2012) phosphodiester bridge to different labels - Naphthylthiourea-modified FT-ICR osensor for Hg2+ in (Chen et al., 2011d) permethylcyclodextrin water and living cells Perylene bisimide-bridged For selective sensing of aniline vapour for MALDI (Jiang et al., 2011a) bis(permethyl- -CDs quality control of food -Conjugated molecules With molecular wire for synthesis of covered by permethylated TOF (Terao, 2011) mono-molecular electronic devices cyclodextrins Slipped-cofacial Aqueous phthalocyanine (Zn[Pc(SO3)4]). phthalocyanine dimer as a J-Type slipped-cofacial dimer prepared shallow inclusion complex TOF (Morisue et al., 2012) with by the aid of host-guest with per-O-Me- - interactions cyclodextrin Tin-containing cyclodextrins TOF As potential enzyme models (Zhou et al., 2012c) Rotaxanes Synthesis of a mechanically switchable Cobalt TOF bistable [1]rotaxane, containing (Gao et al., 2011) coordinated [1]rotaxane azobenzene modified cyclodextrins

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TABLE 36. (Continued) Six -cyclodextrins, PEG axle, end caps applied with click chemistry from nitrile Cyclodextrin-based TOF (Jang et al., 2012) polyrotaxanes N-oxide prepared from 2-hydroxy-1- naphthaldehyde Pseudorotaxane with fullerene derivative Fullerene- -cyclodextrin TOF (Ikeda et al., 2011) and two -cyclodextrin molecules Two isomers of 6-stilbene-amide- - Pseudo[2]rotaxane with cyclodextrin show different inclusion TOF (Wang et al., 2011n) cyclodextrin derivatives behaviors upon complexation with an alkyl chain bearing pyridinium end caps Polymers Acrylamide- and TOF methacrylamide-type (HABA/1,1,3, Synthesis of biohybrid glycopolymers (Ghadban et al., macromonomers with 3-tetramethyl- capable of ionotropic gelation 2012) alginate-derived guanidine oligosaccharides Carbohydrate- L-, R-TOF Synthesis via organocatalyzed ring- (Miao, et al., 2011) functionalized polylactides (dithranol) opening polymerization Cellulose with thymidineand/or trimethyl- To solubilize single walled carbon (Kawagoe et al., TOF ammonium appendages at nanotubes 2011) C6 With cellobiose acetate or cellulose Comb-shaped graft (Enomoto-Rogers et TOF triacetate side-chains prepared via click copolymers al., 2012) chemistry Comb polymer decorated TOF/TOF Synthesis by carbohydrate-initiated (Weber et al., 2012) with glucose (DCTB) cationic ring-opening polymerization Co-polymer with cyclodextrin and adamantly Self-assembly by insertion of adamantine (Stadermann et al., TOF (HABA) end-functionalized into cyclodextrin 2011) monomers Use of Candida antarctica B lipase for synthesis of oligomeric compounds with Co-polymer of 3- ring-opened gluconolactone units (Kakasi-Zsurka et al., hydroxybutyric acid and D- TOF (DHB) included in the chain, without previous 2011) glucono- -lactone derivatization of the sugar, or activation of the acid monomer. Core-shell nanoassemblies based on -CD-containing TOF Hydrophobic molecules resided (Zhang & Ma, 2011) block copolymer and (dithranol) preferably in the cores of assemblies poly( -benzyl L-aspartate) Synthesized from cyclodextrin-(SH) by a Cyclodextrin-centred star 7 TOF combination of thiol-ene click and ring (Zhang et al., 2012e) polymers opening polymerization -CD plus poly(N-Pri- Three-arm star copolymer. Thermally acrylamide)and poly(N,N- TOF (CHCA) (Zhang et al., 2012b) reversible hydrogel di-Me-acrylamide Diblock copolymers of Synthesis of diblock methylcellulose regioselectively methylated (Nakagawa et al., TOF derivatives with regioselective cellulose and unmodified 2011b) functionalization patterns cello-oligosaccharides Use of cross-linked mutant (Nakamura et al., Fibrous cellulose TOF endoglucanase II to produce fibrils rather 2011a) than plate-like crystals Glyconanocapsules TOF Click chemistry with di-triazolo-sucrose (Roux et al., 2012) Synthesis, cloud point tuning, and lectin Glyco-poly(2-oxazoline)s TOF (DCTB) (Kempe et al., 2011) binding Glycosylated poly- Synthesis and characterization of an (naphthalene/phenylene) R-TOF (DHB) (Nagy et al., 2011) amphiphilic blue-light-emitting polymer copolymer Synthesis, secondary and self-assembly Helical polypeptide-grafted TOF structures, and inclusion complex with (Lin et al., 2012b) cyclodextrin bioconjugates guest compounds Hyperbranched polymers TOF (CHCA) Spontaneously forms supramolecular from poly(N-isopropyl- cation- thermoresponsive hyperbranched acrylamide) containing one exchange resin polymers via molecular recognition (Ge et al., 2011) adamantyl and two - to improve between adamantane and -cyclodextrin cyclodextrins ionization moieties

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TABLE 36. (Continued) Synthesis of core-shell structured PEG- - cyclodextrin co- L-TOF nanoassemblies with copolymer and (Zhang & Ma, 2011) polymers (dithranol) poly( -benzyl L-aspartate) via host-guest complexation Enzymatic polymerization to alternating N-Phthaloyl chitin polymer TOF N-phthaloyl chitin derivatives catalyzed (Ohmae et al., 2011) by chitinase TOF (DHB), Poly-N-acetyllactosamine Combinatorial one-pot synthesis with glycans (free (Rech et al., 2011) oligosaccharides Leloir-glycosyltransferases and per-Me) Poly(3-hexylthiophene)- block-poly(3-O- TOF For synthesis of fluorescent nanoparticles (Aissou et al., 2011) methacryloyl-D-Galp) Poly-O-methyl-[n]- TOF Synthesis and characterization from a D- (Kolender et al., polyurethane (dithranol), EI glucamine-based monomer 2011) Polysaccharide- -PEG (Novoa-Carballal & TOF Synthesis by the oxime click reaction block copolymers Antibiotics and other drugs Synthesis of analogue with significantly Bleomycin analogues MALDI (Huang et al., 2012a) improved DNA cleavage activity GilGT, the glycosyltransferase involved in C-glycosylation during gilvocarcin (Shepherd et al., Gilvocarcin analogues TOF biosynthesis used to transfer other 2011) hexoses to gilvocarcin Globotriose-chitosan TOF (DHB), Novel inhibitor of shiga toxins produced (Li et al., 2012f) conjugate FAB by Escherichia coli MALDI- Use of engineered glycosyltransferase to (Zhou & Thorson, Glycosylated mitoxantrone FTMS add -D-Glc 2011) Isoindole and benzoisoindole derivatives TOF Good antibacterial and antiviral activities (Sipos et al., 2012) of teicoplanin pseudoaglycon Potent antitumor angucycline Landomycin A MALDI antibiotic. 63 steps. MALDI for di- and (Yang et al., 2011e) penta-saccharides Cyclosophoraoses [cyclic -(1,2)- Naproxen complexed with TOF glucans] from Rhizobium leguminosarum (Kwon et al., 2012b) cyclosophoraoses biovar trifolii TA-1. For solubilization Neomycine B (ring II) + Strongly inhibits Tat-mediated MALDI (Das et al., 2012) peptide transactivation of HIV-1 transcription Neomycin-neomycin dimer TOF High affinity for AT-rich DNA duplexes (Kumar et al., 2011b) Pyrimethamine solubilised TOF Dimers from Shinorhizobium meliloti (Kim et al., 2012f) with succinoglycan dimers Microarrays, quantum dots, nanoparticles etc. Blockwise alkylated For live cell labelling with low (Kamitakahara et al., tetrasaccharide-organic TOF cytotoxicity 2012) quantum dot complexes Carbohydrates functionalized TOF (DHB, For attachment to polystyrene of glass (Weissenborn et al., with trityl groups 4-Cl-CCA) slides 2012) TOF Charge modified particles Modified with thiolated oligosaccharides (Aljabali et al., 2011) (THAP) Cysteamine conjugated TOF For preparation of gold nanoparticles (Unak et al., 2012) mannose triflate Cowpea mosaic virus TOF (Alibaud, et al., polyelectrolyte-templated Modified with thiolated oligosaccharides (THAP) 2011) gold nanoparticles TOF (Anthranilic Synthesis. Determination of binding acid/ towards Pseudomonas aeruginosa lectin (Gerland et al., Fucosylated glycoclusters nicotinic B using a DNA-based carbohydrate 2012a) acid, HPA, microarray THAP) -Glucopyranosylamide 4 For preparation of mixed self-assembled (Hassan & Maltman, TOF bearing 1,2-dithiolane group monolayers on gold 2012) 1 3- and 1 6-glucose MALDI, To define β-glucan ligands for dectin-1 (Palma et al., 2012) sequences GC/MS

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TABLE 36. (Continued) For the study interactions between Glycans terminating in R-TOF/TOF sialylated glycans and proteins and (Song et al., 2011e) various sialic acids viruses Glycolipid glycans + To study interaction with Vibrio cholera TOF (Seo et al., 2011a) aminophenyl disulfide toxin by force analysis Graphene oxide-based TOF With Glc , click chemistry. Self-assembly (Cheng et al., 2012) hydrogels and organogels 2 Homo- and Synthesis and binding to Pseudomonas (Gerland et al., hetero-functionalized TOF (HPA) aeruginosa lectins PA-IL and PA-IIL 2012b) glycoclusters Copper-catalyzed Huisgen cycloaddition Lectin-adhesive nanoparticles TOF of PEG- -tetra(phenylene) conjugates of lactose and N-acetyl-glucosamine ligands Maltoheptose linked to peracetylated (de Medeiros Maltoheptose nanoparticles TOF maltoheptaose - self assembles into Modolon et al., 2012) nanoparticles Surface modification of polymeric TOF (trans- Polymeric microspheres microspheres using glycopolymers for (Pfaff et al., 2011) 3-(3-IAA) biorecognition Sugar-chain-immobilized TOF Used for probing lectin and cells (Shinchi et al., 2012) fluorescent nanoparticles Sialooligosaccharides bound TOF Enzymatic synthesis. For cell adhesion ( to N-Ac-lactose on gold (THAP) studies TOF Use of covalent thiourea bridging on (Grabosch et al., Thiourea adducts (CHCA) polystyrene microtiter plates 2012) For glycoarray fabrication on both S-Tritylated -D-mannosides TOF (Wehner et al., 2012) polystyrene and gold From p-(4-oxopentanamido)-phenyl Various (Glc, Man, Fuc, glycosides, plus 11-mercapto- (Ohyanagi et al., GlcA, GlcNAc, GalNAc, TOF undecylphosphorylcholine. Use in 2011) Lac, Neu5Ac) imaging 89Zr-Labeled dextran MALDI For in vivo macrophage imaging (Keliher et al., 2011) nanoparticles Miscellaneous Complex which acts as an excellent -D-Allopyranoside-grafted MALDI pH- -off- (Zhao et al., 2012b) ruthenium(II) complex switch TOF Highly polar carbohydrates shown to Carbohydrate-oligonucleotide conjugates (THAP, stack onto DNA duplexes via CH/ (Lucas et al., 2011) NH4Citrate) interactions Contain chiral cavity. Act as catalysts in Chiral lanthanoid dimers thio-Michael addition reactions as well as ligated by carbohydrate-based MALDI metal-based luminescence in the case of (Gee et al., 2011) diketonates europium Complexes of highly succinylated Cyclosophoraoses from Sinorhizobium (Kwon & Jung, TOF cyclosophoraoses with 4'- trifolii TA-1. Product masses to 55kDa 2011a) hydroxyflavanone Curcumin-hyaluronic acid To improve solubility of curcumin for (Manju & TOF conjugates drug use Sreenivasan, 2011) Dimeric glycomimetic R-TOF/TOF e.g. Two N-acetylchitobiose residues with ligands of NK cell activation (DHB) hydrocarbon linkers 2011) receptors Galactose-linked Synthesis and screening against (Mugunthan et al., TOF/TOF nitroimidazoles/triazoles Mycobacterium tuberculosis 2011b) Perylene diimide dye plus For stable photosensitized material in TOF/TOF (Dinçalp et al., 2012) GlcOAc photodynamic therapy Sugar-derived chiral (Mugunthan et al., TOF/TOF As potential antimycobacterial agents nitroimidazoles 2011a) Used to reveal critical enzyme-substrate UDP-Galactofuranose TOF (DHB) interactions in GlfT2-catalyzed (Poulin et al., 2012) analogs mycobacterial galactan assembly UDP-xylose and UDP- (Rosenberger et al., TOF (DHB) Synthesis in Trichomonas vaginalis galactose 2012) Uridine- -O-(2- Enzymatic synthesis with MALDI-TOF thiodiphospho)-N- TOF/TOF (Cai et al., 2011c) to assay for glycosyltransferase activities acetylglucosamine

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TABLE 37. Use of MALDI MS to study methods for general synthesis Compound Methodsa Notes Reference O-Alkylamino- TOF (DHB) Major increases of the reactivity and selectivity in (Jackowski et al., glycosides FAB, EI aminoglycoside O-alkylation due to fluoride ions 2012) Anionic glycans with By thermostable phosphorylase-catalyzed - (Umegatani et al., TOF (DHB) non-reducing GlcA glucuronylation of maltooligosaccharides 2012) Aromatic esters of (Croitoru et al., TOF (DHB) Use of sol-gel immobilized commercial lipases sugar alcohols 2011) Azidochlorination of Reaction of protected glycals with sodium azide, (Plattner et al., TOF (DHB) glycals ferric chloride, and hydrogen peroxide 2011) Accelerated O-glycosylation under frozen (Ishiwata et al., Complex N-glycans TOF conditions 2012) Modification of the secondary face by copper- (Ward & Ling, Cyclodextrins TOF (DHP) catalyzed Huisgen 1,3-dipolar cycloaddition 2011) Use of 1 3- and 1 6-fucosyltransferases for Fucosylated N-glycans TOF (Serna et al., 2011) core fucosylation Functionalized (Mergy et al., TOF Synthesis via thiol-ene chemistry carbohydrates 2012) Galacto- Use of -galactosidase inclusion bodies containing TOF (Lee et al., 2011f) oligosaccharides Escherichia coli cells (Garcia-Martin et Glycopeptides TOF (DHB) Solid-phase synthesis using microwave irradiation al., 2012) By ring opening polymerization of O- Glycopeptides TOF (Pati et al., 2011) glycosylated- -amino acid N-carboxyanhydride Synthesis of N-glycopeptides by convergent N-Glycopeptides TOF assembly 2012) Use of engineering E. coli to execute the initial (Henderson et al., Glycoproteins TOF steps of human, mucin-type O-glycosylation 2011b) (Hudak et al., Glycoproteins MALDI Oxime linkage. MALDI-MS to study stability 2011) -Glycosides TOF Use of 2-azido-2-deoxythioglycosides (Mong et al., 2012) Use of saccharide primer and Madin-Darby canine (Shimura et al., Glycosphingolipids TOF kidney cells 2012a) TOF Concise synthesis of glycosphingolipids based on (Velasco-Torrijos Glycosphingolipids (CHCA) aspartic acid building blocks et al., 2012) Glycosyl sulfonium (Nokami et al., TOF As storable intermediates for glycosylations ions 2011) R-TOF Immunomodulatory Use of charged hexosaminides as new substrates (DHB, disaccharides for -N-acetylhexosaminidase-catalyzed synthesis 2011) CHCA) Selective removal of the (2-naphthyl)methyl Mono- and di- R-TOF protecting group in the presence of p- saccharides (THAP) 2012b) methoxybenzyl group by catalytic hydrogenation (1 2)-Linked Use of ionic liquid support for the synthesis of TOF (Ma et al., 2011a) nonamannoside large and complex oligosaccharides Use of glycosyl ortho-hexynylbenzoates as donors N-O-linked glycans MALDI (Yu et al., 2012a) under the catalysis of PPh3AuOTf O-Glycans with Use of CHO IdID cell line fed with GalNR (Pouilly et al., unnatural GalNR TOF molecules so that they could be incorporated into 2012a) groups O-glycans New method for regioselective glycosylation (Matwiejuk & Oligosaccharides TOF (DHB) employing saccharide oxyanions Thiem, 2011) (Uchinashi et al., Oligosaccharides TOF C5-acetamide sialic acid donor for -selective sialylation 2011) TOF/TOF Use of anomeric sulfonium ions as glycosyl Oligosaccharides (Fang et al., 2012) (DHB) donors (Durantie et al., Oligosaccharides MALDI Fluorine-directed -galactosylation 2012) Acceptor-influenced and donor-tuned base- (Boettcher et al., Oligosaccharides TOF (DHB) promoted glycosylation 2012) Use of N-benzenesulfonyl-based ionic-liquid mass Oligosaccharides TOF (DHB) spectroscopy label (I-Tag2) for covalent (Galan et al., 2012) attachment to substrates Method for overexpression of 13C-labeled (Kamiya et al., Oligosaccharides TOF oligosaccharides using genetically engineered 2011) Saccharomyces cerevisiae cells

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TABLE 37. (Continued) 1,2-Oxazoline One-step synthesis and application to (Noguchi et al., derivatives of TOF (DHB) chemoenzymatic -N-acetylglucosaminidation of 2012) unprotected sugars disialo-oligosaccharide Poly LacNAc Use of Helicobacter pylori 1,3-N- TOF (Peng et al., 2012b) extensions acetylglucosaminyltransferase R-TOF Use of a -xylosidase from Aspergillus awamori (Kurakake et al., Sugar fatty acid esters (DHB) for transxylosylation 2011) From propargyl glycosides by use of alkynophilic (Vidadala et al., Thioglycosides TOF gold catalyst 2012) Use of broad-specificity xyloglucan glycosynthase (Spadiut et al., Xyloglucans TOF (DHB) and a fucosyltransferase 2011) Chemistry based approach for degradation of (Takahashi & Various TOF target-oligosaccharides using photo-activatable Toshima, 2012a) organic small molecules aFormat (not all items present): MALDI method (matrix). “MALDI” used when instrument not speciﬁed.

TABLE 38. Use of MALDI MS to study carbohydrate reactions Reaction Methodsa Reference Accelerated enzymatic galactosylation of N-acetylglucosaminolipids in TOF/TOF (Noble et al., 2012) lipid microdomains (Lumholdt et al., -Amylase mediated hydrolysis of cyclodextrins TOF (CHCA) 2012) Azide-alkyne cycloaddition for stitching a monosaccharide to a linear (Pathigoolla et al., TOF oligomer 2012) Biocatalytic acylation of sugar alcohols by 3-(4-hydroxyphenyl)propionic (Croitoru et al., TOF acid 2012) (Gandolfi et al., Chemoenzymatic deacylation of ramoplanin TOF 2012) Divergent behavior of glycosylated threonine and serine derivatives in (Zhang et al., TOF solid phase peptide synthesis 2012k) Effect of substituents of the neighboring ring in the conformational - TOF equilibrium of iduronate in heparin-like trisaccharides al., 2012) TOF/TOF Enzyme-catalyzed cross-linking of feruloylated arabinan from sugar beet (Zaidel et al., 2011) (CHCA) Genetic engineering of Escherichia coli to produce Man GlcNAc (Valderrama- 3 2 TOF/TOF glycoproteins Rincon et al., 2012) (Chung et al., Glucan adsorption on mesoporous carbon nanoparticles TOF (DHB) 2012b) (Hidaka et al., Mild acid hydrolysis of sphingolipids to give lysosphingolipids TOF 2012) Phenol O-glycosylation with glycosyl imidates MALDI (Li et al., 2012g) (Takahashi et al., Photodegradation of oligosaccharides by a fullerene-boronic acid hybrid TOF 2011a) Production of clickable surfaces for chemical modification of cellulose MALDI (Xu et al., 2012a) Stereoelectronic effects found to determine oxacarbenium vs -sulfonium TOF (DHB) (Boltje et al., 2011) ion mediated glycosylations TEMPO-mediated glycoconjugation - controlled synthesis of TOF (Ma et al., 2011c) polysaccharide conjugates Use of the surfactant ionic liquid [R4N] [AOT] as a mild glycosylation TOF (DHB) (Galan et al., 2011) promoter Use of -CD inclusion complexes to study advanced oxidation processes (Bokare & Choi, TOF (CHCA) based on the Cr(III)/Cr(VI) redox cycle 2011) aFormat (not all items present): MALDI method (matrix). “MALDI” used when instrument not speciﬁed. ing, particularly from the larger glycans, can still present imaging. Unfortunately, some structural analyses of carbohy- problems. Methods are now available for production of negative drates leave much to be desired and there are many incorrect ions from neutral glycans; fragmentation of these species structures reported in the literature. Much of this can be attributed gives considerably more information than most positive-ion to assumptions made between a simple mass measurement and methods. Permethylation seems to be becoming more widely structure, particularly when structures are selected directly from used and has the advantage of enabling larger structures to be databases. There is no one mass spectrometric technique that can seen than with analysis of native compounds. New techniques, identify all structural features of carbohydrates; MALDI and such as ion mobility, have emerged to complement both MALDI electrospray results still have to be augmented with data from and electrospray. Other growing areas are glycan arrays and techniques such as GC/MS and exoglycosidase digestion to

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TABLE 39. Use of MALDI MS for studies on glycodendrimers and glycoclusters Scaffold Sugar Methodsa Notes Reference Synthesis of high-affinity multivalent wheat germ (Beckmann et Amines (various) Chitobiose FT-ICR agglutinin ligands by one-pot al., 2012) click reaction (Lampropoulou (6-aminoethyl- GlcNAc, mannose, & amino-6-deoxy)- - TOF For targeting bacterial lectins glucose Yannakopoulou, CD 2011) Incorporation into liposomes. TOF (Novakova et al., Azaphthalocyanines Galactose Effect of number of glycans (DCTB) 2012) on properties Bacteriophage Q LacNAc and (Rhee et al., MALDI For photodynamic therapy virus-like particles LacNAc-sialic acid 2012) Synthesised by click (Galante et al., Calix[4]arene Lactose TOF chemistry. Tripanocidal 2011) activity Synthesis by Huisgen (Matsuoka et al., Carbosilane Lewisx determinants TOF cycloaddition 2012) Triazole as branching unit. 12- (Rajakumar & 1,3,5-Carboxamide -D-Glcp TOF, FAB 18 Glcp units Anandhan, 2011) Cavitand on a Forms complexes with resorcinarene hydrophobic small molecules. (Ryan & Rebek, Glucose TOF platform with Used to observe caviplexes in 2011) aromatic subs. human serum (O-/N-linked - Synthesis of glycoclusters maltoside and O-/N- with high structural (Negishi et al., Cellulose TOF linked -lactoside) at homogeneity using click 2011) 6C positions chemistry For targeted two-photon (Wang et al., Complex - 3 arms Glucosamine TOF fluorescence imaging 2012c) Synthesis of cyclodextrin- (Decroocq et al., Cyclodextrins Aminoglucose TOF based iminosugar click 2011) clusters For probing carbohydrate- - -CD Lactose , Glucose TOF (DHB) lectin recognition in 14 8 et al., 2012) heterogeneous environments -Cyclodextrin -Moscoso Mannose TOF For site-specific gene delivery (CH3(CH2)4CO)14 et al., 2011) Galactose, mannose, L-TOF 16 Sugars conjugated by (Bossu et al., Cyclopeptide lactose, Gal-GalNAc (DHB) oxime chemistry 2011) Synthesis by click chemistry. (Yang et al., Cyclotriveratrylene Glucose, galactose TOF Interaction with fullerene 2012b) TOF (3-OH- New method for spatial picolinic (Schlegel et al., Duplex DNA Lewisx trisaccharide alignment of carbohydrates on acid (DNA), 2011) a scaffold THAP) Synthesis of tetravalent Ethylene glycol (N-Ac- R-TOF glycoclusters as probes for bis( -aminoethyl (Ogata et al., Lactosamine) , (THAP/NH Sambucus sieboldiana ether)-N,N,N ,N - 1,2 4 2012) Neu5Ac -citrate) agglutinin. Characterization of tetraacetate binding properties For inhibition of liposaccharide L-glycero-D-manno- (Durka et al., Fullerene TOF heptosyltransferase WaaC: heptopyranoses 2012) New mode of glycosyltransferase inhibition TOF/TOF Synthesis of dodecavalent (Cecioni et al., Fullerene Galactose (dithranol) glycoclusters and binding 2011a) ESI, FAB properties to a bacterial lectin TOF/TOF Use of photoinduced thiol-ene Glucose, mannose (MTB, (Lo Conte et al., -ene coupling for exhaustive 48 lactose, GlcNAc HABA, 2011) glycosylation dithranol) Mannose (C H For study of mannose-lectin (Wang et al., Glucose 3 6 MALDI linker) interactions 2011b)

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TABLE 39. (Continued) Mannose (C H For study of mannose-lectin Glucose 3 6 TOF (Wang, 2011) linker) interactions Mannose- (Kauscher & adamantane -Cyclodextrin TOF Interaction with lectin Con-A Ravoo, 2012) conjugates Synthesis by use of R-TOF Glucose, mannose photoinduced free-radical (Lo Conte et al., Octasilsesquioxane (CHCA, lactose, GlcNAc thiol-ene coupling. Lectin 2012) sinapinic) binding Synthesis and biophysical (Trastoy et al., Octasilsesquioxane Mannose TOF study 2012) Up to 83 sugars. As hepatic (Medina et al., PAMAM GalNAc TOF cancer cell-targeted carriers 2011) Polygluconolactone- (Zhang et al., PAMAM TOF (DHB) As potential anticancer agent methotrexate 2011m) Dendrimers bearing tris- (Schlick et al., PAMAM Mannose TOF mannosides by click chemistry 2011) Synthesis without protecting (Clayton et al., PAMAM Sialic acid TOF groups. Anti-HIV 2011) Effects of neighbouring (Liang et al., Peptide Mannose TOF glycans on antibody 2011a) carbohydrate interaction Mannose, lactose, Fluorophore-labelled. (Tian et al., Peptide GlcNAc, fucose, TOF Synthesis and lectin binding 2011) Neu5Ac-LacNAc properties Convergent synthesis of (Kowalczyk et Peptides Mannose TOF glycodendropeptides by click al., 2012) chemistry approaches Mannobiose, For construction of (Tian et al., Peptides TOF LacNAc microarrays 2012) Synthesis, and binding to (Xue et al., Pertlene Neomycin TOF human telomeric DNA 2011a) As new candidates for (Wang et al., Phenylporphyrins Mannose TOF retinoblastoma by 2012i) photodynamic therapy Compound with two CD TOF Poly(N-iso-propyl- moieties spontaneously forms (CHCA + acrylamide) with supramolecular (Ge, et al., 2011) -Cyclodextrin DOWEX one adamantly group hyperbranched polymers in 50W-X8) aqueous solution As potent inhibitors of DC- TOF (DHB, (Luczkowiak et Polyesters Pseudosaccharides SIGN dependent Ebola sinapinic al., 2011) pseudotyped viral infection As photodynamic therapy Glucose, mannose, (Garcia et al., Porphyrin TOF (DHB) agents. Synthesis by click galactose 2011) chemistry Porphyrin plus Glucose, galactose or As photosensitizers for (Ballut et al., TOF glycine mannose targeting cancer cells 2011) Synthesis of shape amphiphiles based on TOF/TOF (Zhang et al., Silsesquioxanes Glucose functional polyhedral (DCTB) 2011g) oligomeric silsesquioxane end-capped poly(L-lactide) Stearylamide lysine TOF (s- Third generation - 16 sugar (Han et al., Cellobiose dendrimer DHB) residues, antiviral 2012b) Triamino- TOF (Park et al., -Cyclodextrin Synthesis by click chemistry triethylanine (CHCA) 2012b) Trimesic acid (1,3,5- Galactose (up to 27 TOF As bacterial (Pseudomonas (Chabre et al., benzene- residues) (sinapinic) aeruginosa) lectin inhibitors. 2011) tricarboxylic acid) Star-shaped glycosylated (Wang et al., Triphenylamine Glucose TOF conjugated oligomer for two- 2011d) photon fluorescence imaging Click chemistry. Synthesis and (Miura et al., Trivinyl benzene Sulfonated-GlcNAc TOF observation of a reduction in 2012) nanofiber formation

114 Mass Spectrometry Reviews DOI 10.1002/mas TABLE 39. (Continued) With two-photon absorption Zinc-porphyrin properties as potential (Achelle et al., Mannose TOF oligomers photosensitizing agents for 2011) photodynamic therapy For use as a photosensitizer in Zinc(II)- (Aggarwal et al., Thioglucose (8 units) TOF photodynamic therapy for Phthalocyanine 2011) cancer R-TOF Prepared by click chemistry (Cecioni et al., Various Galactose (CHCA) for probing lectin selectivity 2011b) Reversed compounds Synthesis of nanoparticles for -Cyclodextrin Poly-( -amino esters) TOF sustained drug delivery across (Gil et al., 2012) the blood-brain barrier To study mono- and TOF Sucrose Peptides multimeric binding of the (Rao et al., 2011) (sinapinic) peptides aFormat (not all items present): MALDI method (matrix). “MALDI” used when instrument not speciﬁed.

TABLE 40. Use of MALDI MS to study carbohydrate-protein conjugates Sugar Protein Techniquea Notes Reference For preparation of a specific Asiaticoside (steroid TOF (Juengwatanatrakul BSA monoclonal antibody for the glycoside) (sinapinic) et al., 2011) development of an ELISA For development of Bacoside A3 (steroid TOF immunosorbant assay for (Tothiam et al., BSA glycoside) (sinapinic) determination of jujubogenin 2011) glycosides TOF Synthesis, structure and surface Chitosan BSA (He et al., 2012a) (sinapinic) charges Clostridium difficile Phosphorylation of the repeating (Adamo et al., PSII cell wall CRM TOF unit shown to be essential for the 197 2012) polysaccharide induction of antibodies Squaric acid linker. To prevent Ribonuclease TOF (Prashar et al., -Cyclodextrin aggregation and to increase A, lysozyme (sinapinic) 2011) thermal stability To form modified sialylated Diazirine-modified Jurkat cell (Bond et al., TOF glycoconjugates for photo-cross- ManNAc glycoproteins 2011b) linking to interacting molecules Galacturonate- Synthesis of carbohydrates and (Pourcelot et al., containing MALDI conjugation to protein and fatty 2011) disaccharides acids Gal -Glc -Man - TOF/TOF To investigate mechanisms of 1 1 9 RNase (Amin et al., 2011) GlcNAc2 (DHB) molecular chaperones Glycan array used to identify GalNAc 1 4(Fuc (Aranzamendi, et BSA TOF/TOF glycan as potential antigen for 1 3)GlcNAc-R al., 2011) serodiagnosis of trichinellosis TOF Cholesterol promotes formation of (Hirasawa et al., Glucose/cholesterol BSA (sinapinic) AGEs 2011) Analysis of commercial sample for L-TOF (Plesner et al., Glyco-PEG Factor VIIa measurement of hydrodynamic (CHCA) 2011) volume GM3 (Neu5Ac- Keyhole Synth. of 4 p-substituted Ph-acyl 2 3-Gal- 1 4- limpet TOF, TLC derivatives to improve (Yu et al., 2011b) Glc) haemocyanin immunogenicity Diphtheria Group A toxin mutant L-TOF/TOF Synthesis and immunoprotective (Kabanova et al., Streptococcus CRM197, (sinapinic) efficacy (vaccine candidate) 2011) oligosaccharide HSA Hexasaccharide from hypervirulent Diphtheria L-TOF/TOF As possible oligosaccharide- (Oberli et al., 2011) ribotype 027 of toxin, CRM197 (sinapinic) conjugate vaccine Clostridium difficile Inner core of Containing 4-amino-4-deoxy-L- TOF (Blaukopf et al., Burkholderia and BSA arabinose epitopes as (sinapinic) 2012) Proteus LPS immunoreagents Inner core oligosaccharide of Diphtheria TOF Use of three conjugation methods. (Cox et al., 2011) Moraxella toxin, CRM197 (sinapinic) As vaccine antigens catarrhalis

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TABLE 40. (Continued) Inner core of L-TOF Approx 10 carbohydrate molecules (St. Michael et al., Mannheimia CRM 197 (sinapinic) attached. As vaccine 2011) haemolytica Trypsin, Glu C, V8, Development of method to (Jahouh, et al., Lactose BSA TOF/TOF determine the glycosylation sites 2012) (CHCA), (lysine residues) LC-MS/MS TOF/TOF As vaccine candidate against (Adamo et al., Laminarin fragments CRM 197 (DHB) Candida albicans 2011) TOF/TOF Use of bacterial enzymes for Lewisx antigen AcrA (Hug et al., 2011) (CHCA) glycoprotein synthesis LPS from Bordetella L-TOF (Kubler-Kielb et pertussis and B. BSA For anti-pertussis vaccine (sinapinic) al., 2011) bronchiseptica LPS from TOF Synthesis and immunogenicity in (Monteiro et al., BSA Helicobacter pylori (sinapinic) mice 2011) LPS (commercial, TOF Practical details for conjugation (Kubler-Kielb, BSA various sources) (sinapinic) using oxime chemistry 2011) Structurally diversified linker -Mannan TOF shown to enhance immune (Lipinski et al., CSA disaccharide (sinapinic) response to small carbohydrate 2011) hapten For later labelling with 68Ga as a Mannose HSA TOF/TOF lymph node imaging agent for (Choi et al., 2011) positron emission tomography Human acid Comparison of various synthetic (Mannose) TOF (Zhou et al., 2011) 6 -glucosidase methods 6-O-Me-D-glycero- - L-gluco-heptopyranose from Paper mainly concerned with Campylobacter jejuni BSA MALDI (Peng et al., 2011) synthesis of carbohydrate NCTC 11168 capsular polysaccharide O-chain from Hafnia TOF/TOF As new functional ligands for (Swierzko et al., BSA alvei 1200 (THAP) ficolin-3 2012) MUC1 glycopeptide Synthesis of potential vaccine and (Hoffmann- with -deoxy- - BSA TOF binding to anti-MUC1-mouse & Johannesy, fluoro-Thomsen antibodies 2011) Friedenreich antigen Induced a strong immune response (Gaidzik et al., MUC1 glycopeptide BSA TOF (DHB) against breast tumor tissues 2011) TOF (DHB, Synthesis and evaluation as MUC1 glycopeptide BSA (Cai et al., 2011b) CHCA) vaccines Non-Me disaccharide TOF/TOF Synthesis and immunochemical (Milhomme et al., analogue of anthrax BSA (sinapinic) evaluation 2012) tetrasaccharide Oligosaccharide BSA and Up to 15 sugars conjugated. To fragments of E. coli TOF (Pozsgay et al., diphtheria demonstrate cross-reactivity O148 OSP, up to a (sinapinic) 2012) toxin between polysaccharide antigens dodecasaccharide Per-OMe- - TOF To introduce binding site for (Kitagishi et al., BSA cyclodextrin (CHCA) porphyrins 2012) (Pedersen et al., Plant polysaccharides BSA TOF To construct microarrays 2012b) BSA, To utilise naturally-occurring L- Rhamnose TOF (Chen et al., 2011a) ovalbumin Rha antigens for cancer treatment TOF/TOF Sialylated MUC1 Effect of sialylation pattern on BSA (DHB, (Cai et al., 2012) glycopeptide immune response CHCA) 6-SO3-GlcNAc-containing sugar 6-Sulfated GlcNAc R-TOF-TOF shown to mimic the sulfated BSA (Couto et al., 2012) mimics (sinapinic) cruzipain epitope that plays a central role in immune recognition Sulfo-LewisA and (Singh et al., Ovalbumin MALDI For targeting mannose receptor (GlcNAc)3 2011c)

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TABLE 40. (Continued) As a new carrier for tumor Tobacco TOF Tn antigen associated (Yin et al., 2012b) mosaic virus (sinapinic) carbohydrate antigens Vibrio cholerae O- SELDI Squaric acid linker, as potential BSA (Xu et al., 2011a) SP-core antigen (sinapinic) vaccine General procedure for synthesis of TOF neoglyco-proteins and (Zhang & Various BSA (sinapinic) immobilization on epoxide- Gildersleeve, 2012) modified glass slides Various up to MW TOF, LC- Synthesis by oxime ligation (Styslinger et al., Hemoglobin 10,000 MS/MS alternative to PEGylation 2012) aFormat: MALDI method (matrix). MALDI used when instrument not stated. Other methods.

TABLE 41. Use of MALDI MS for examination of biochemical reactions Compound Methodsa Notes Reference -1,6-N- Model for -1,6-N-acetylglucosamine oligomer R-TOF (Fazekas et al., Acetylglucosamine hydrolysis catalysed by DispersinB, a biofilm (THAP) 2012) oligomer degrading enzyme Metabolic labeling to enable selective Diazirine-modified (Yu et al., R-TOF (DHB) photocrosslinking of O-GlcNAc-modified GlcNAc derivatives 2012d) proteins to identify their binding partners Evaluation of GalNAc analogues as substrates Glycopeptides, (Pouilly et al., R-, L-TOF for enzymes of the mammalian GalNAc salvage glycoproteins 2012b) pathway Metabolic labeling of Caenorhabditis elegans (Burnham- Glycoproteins TOF/TOF primary embryonic cells with azido-sugars as a Marusich et al., tool for glycoprotein discovery 2012) Glycoproteins from Metabolic labelling with azido-modified sugars (Hart et al., human mesenchymal MALDI and click chemistry detection for markers of cell 2011) stem cells differentiation TOF Arginine-specific mono ADP-ribosylation in (Castagnini et Human -defensin (sinapinic), vitro of antimicrobial peptides by ADP- al., 2012) peptides ribosylating toxins Mutation of N-glycosylation sites to determine (Ishino et al., Interleukin-5 receptor TOF effect on function 2011) TOF Introduction of O-glycans in the non-core region (Yanaka et al., Interleukin-11 (sinapinic), to investigate function 2011) glycoprotein The ppm operon shown to be essential for R-TOF, (Mohiman et al., Lipoproteins acylation and glycosylation of lipoproteins in glycopeptides 2012) Corynebacterium glutamicum MALDI -(1 4)-Mannosyltransferase involved in Methylmannose (DHB),exo- mycobacterial Me-mannose polysaccharide (Xia et al., 2012) polysaccharides glycosidases biosynthesis Glucosylation and other biotransformations of (McCormick et T2 toxins R-TOF (DHB) T-2 toxin by yeasts of the Trichomonascus clade al., 2012) Endoplasmic reticulum-associated degradation (Kukushkin et Tetrasaccharide TOF of glycoproteins shown to occur downstream of al., 2011) processing by endomannosidase UDP-glucuronic acid and Biosynthesis in Bacillus cereus subsp. cytotoxis (Broach et al., TOF UDP-galacturonic acid NVH 391-98 2012) Shown to have anti-inflammatory role in (Jawhara et al., Yeast glucan fractions TOF (DHB) intestinal inflammation 2012) aFormat: MALDI method (matrix), MALDI used when instrument not stated, compounds studied. obtain information on the nature of the monosaccharide building XXV. ABBREVIATIONS blocks of the oligosaccharides. Sialylated and sulfated glycans remain a problem, although sialylated glycans can be handled Excluding most cell lines, protein, and gene names. after suitable derivatization, particularly by permethylation or 2-AA 2-aminobenzoic acid simply by methyl ester or methyl amide formation. The next few 9-AA 9-aminoacridine years are expected to bring many developments, particularly in AAL Aleuria aurantia lectin instrumentation and ionization techniques, that will possibly 2-AB 2-aminobenzamide address some of the problems with carbohydrate analysis ADCC antibody-dependent cell-mediated highlighted above. cytotoxicity

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AEAB 2-amino-N-(2-aminoethyl)-benzamide DDI DNA directed immobilization AGE advanced glycation end products DEAP N,N-diethyl-ammonium AGP a1-acid glycoprotein DESI desorption electrospray ionization Ala alanine DFLNnH difucosyllacto-N-neohexaose AMAC aminoacridone DFpLNH difucosyl-paralacto-N-hexaose AMT 5-amino-2-mercapto-1,3,4-thiadiazole DHA dihydroxyacetone AnCCA (2E)-3-(anthracen-9-yl)-2-cyanoprop- DHAP dihydroxyacetophenone 2-enoic acid DHB dihydroxybenzoic acid (2,5-isomer ANS 2-amino-1-naphthalenesulfonic acid unless specified otherwise) aoWR Na-((aminooxy)acetyl)tryptophanylar- DHBP dihydroxybenzophenone ginine methyl ester DHP dihydroxyacetophenone 2-AP 2-aminopyridine DiNAcBac di-N-acetylbacillosamine AP-MALDI atmospheric pressure MALDI DIT 1,8,9-anthrancenetriol 3-AQ 3-aminoquinoline DMA dimethylaniline Ara arabinose DMB 1,2-diamino-4,5-methylenedioxyben- Arg arginine zene Asp aspartic acid DMF dimethylformamide Asn asparagine DMSO dimethylsulfoxide ATCC American Type Culture Collection DMT-MM 4-(4,6-dimethoxy-1,2,3-triazil-2-yl)-4- ATT 6-azo-2-thiothymine methylmorpholinium chloride AuNPs gold nanoparticles DNA deoxyribonucleic acid Bac bacillosamine (2,4-diamino-2,4,6- DOTA-Gd gadolinium-tetraazacyclododecanete- trideoxy-D-glucose) traacetic acid complex BCSDB bacterial carbohydrate structure database DP degree of polymerization BEMAD b-elimination followed by Michael DPM dolichol-phosphate-mannose (synthase) addition DPPH 2,2-diphenyl-1-picrylhydrazyl BHK baby hamster kidney DTT dithiothreitol BOA O-benzylhydroxylamine EDANS-O-NH2 5-(2-((aminooxyacetyl)amino)ethyla- Boc t-butyloxycarbonyl mino)naphthalene-1-sulfonic acid BODIPY 4,4-difluoro-3a,4a-diaza-s-indacene EDTA ethylenediaminetetraacetic acid BSA bovine serum albumin EI electron impact CD cyclodextrin, circular dichroism or ELIZA enzyme-linked immuno-absorbent assay compact disk Endo-BI-1 (F2, H, S) endoglycosidase-BI-1, (F2, H, S) CDG congenital disorder of glycosylation Endo Tv endo-b-N-acetylglucosaminidase CE capillary electrophoresis EPO erythropoeitin Cer ceramide EPS extracellular polysaccharide CHARMM chemistry at HARvard Molecular ER endoplasmic reticulum Mechanics ERAD endoplasmic-reticulum-associated CHCA a-cyano-4-hydroxycinnamic acid protein degradation CHO Chinese hamster ovary ESI electrospray ionization CID collision-induced dissociation ETD electron transfer dissociation (decomposition) f (as in Galf) furanose form of sugar ring CIEF capillary isoelectric focusing FAB fast atom bombardment Cl-CCA 4-chloro-a-cyanocinnamic acid Fc region of IgG CMBT 5-chloro-2-mercaptobenzothiazole FFPE formalin-fixed, paraffin-embedded CMP cytidine monophosphate Fmoc 9-fluorenylmethoxycarbonyl CNBr cyanogen bromide Fru fructose CNS central nervous system FT Fourier transform Con A concanavalin A Fuc fucose CPP casein phosphopeptides FUT fucosyl transferase CPS capsuar polysaccharide G0, G1, G2 biantennary glycans with zero, one and CSA chicken serum albumin two galactose residues CSF cerebrospinal fluid G0F, G1F, G2F fucosylated biantennary glycans with CV coefficient of variation zero, one and two galactose residues Cys cysteine GAG glycosaminoglycan Da Dalton Gal galactose DBP 3,4-diaminobenzophenone GalA galacturonic acid DC-SIGN dendritic cell-specific ICAM3- GalN galactosamine grabbing nonintegrin GalNAc N-acetylgalactosamine DCTB trans-2-[4-tert-butylphenyl-2- GalNGc N-glycoylgalactosamine methylprop-2-enylidene]-malonitrile GalNR N-alkylgalactosamine

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GalSph galactosylsphingosine IAA indoleacrylic acid GC/MS gas chromatography/mass spectrometry IAM iodoacetamide GD1 ganglioside (Gal-b-(1!3)-GalNAc-b- ICR ion cyclotron resonance (1!4)-Gal-b-(1!4)-Glc-ceramide) IdoA iduronic acid with two sialic acids IgA (E, G, M or Y) immunoglobulin A (E, G, M or Y) GDP guanidine diphosphate ILMAE ionic liquid-based microwave-assisted GilGT glycosyltransferase extraction GIPC glycosyl-inositol-phospho-ceramides IMS ion mobility spectrometry and imaging Glc glucose mass spectrometry GLC gas-liquid chromatography IPG-IEF immobilized pH gradient isoelectric GlcA glucuronic acid focusing GlcCer gulcosylceramide IR infrared GlcN glucosamine IRMPD infrared multiphoton dissociation GlcNAc N-acetylglucosamine ISD in-source decay GlcSph glucosylsphingosine IT ion trap GlcUA glucuronic acid ITMS ion trap mass spectrometry GM genetically modified Kdo 3-deoxy-D-manno-oct-2-ulosonic acid GM1 ganglioside (Gal-b-(1!3)-GalNAc-b- Kdn 3-deoxy-D-glycero-D-galacto-non-2- (1!4)-Gal-b-(1!4)-Glc-ceramide) ulopyranosonic acid with one sialic acid L- linear (as in linear-TOF) GnT GlcNAc transferase Lac lactose GPC gel permeation chromatography LacDiNAc di-N-acetylaminolactose GPG GlycoPep grader LacNAc Gal-b-(1!4)-GlcNAc GPI glycosyl-phosphatidylinositol LAM lipoarabinomannan GPL glycopeptidolipids LARGE like-acetylglucosaminyltransferase GQ1 ganglioside (Gal-b-(1!3)-GalNAc-b- LC liquid chromatography (1!4)-Gal-b-(1!4)-Glc-ceramide) LDI laser desorption ionization with four sialic acids LEISD laser-enhanced in-source dissociation Gro glycerol Lev levulinoyl GSL glycosphingolipid LIFT method for producing fragmentation GT girard’s T (reagent) LM lipomannan GT1 ganglioside (Gal-b-(1!3)-GalNAc-b- LNDFH lacto-N-difucohexaose (1!4)-Gal-b-(1!4)-Glc-ceramide) LNFP lacto-N-fucopentaose with three sialic acids LOS lipooligosaccharide GUI graphical user interface LPS lipopolysaccharides HABA 2-(4’-hydroxyphenyl)azobenzoic acid LSD lysosomal storage disease HCD high energy C-trap dissociation LSI laserspray ionization HEK human embryonic kidney LTA lipoteichoic acid Hep heptose LTQ linear trap quadrupole Hex hexose Lys lysine HexNAc N-acetylhexosamine MA Maackia amurensis lectin hIgG human IgG mAb (MAB) monoclonal antibody HILIC hydrophilic interaction MALDESI matrix-assisted laser desorption chromatography electrospray ionization HIV human immunodefficiency virus MALDI matrix-assisted laser desorption/ HMO human milk oligosaccharides ionization HPA hydroxypicolinic acid MALT mucosa-associated lymphoid tissue HPAEC high performance anion exchange Man mannose chromatography ManNAc N-acetylmannosamine HPLC high performance liquid MCF-7 Michigan Cancer Foundation-7 chromatography (cell line) HPSEC high performance size exclusion MDBK Madin-Darby bovine kidney (cells) chromatography MDCK Madin-Darby canine kidney (cells) HPTLC high performance thin-layer Me-Hex methylhexose chromatography mf-MELDI-MS matrix-free material-enhanced laser HRMALDIMS high resolution matrix-assisted laser desorption/ionization time-of-flight desorption/ionization MS mass spectrometry HRP horseradish peroxidase MHC major histocompatibility complex HRPV haloarchaeal pleomorphic virus MS mass spectrometry HSA human serum albumin MTB 2-mercaptobenzotriazole

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MTT 3-methyl-1-p-tolyltriazene PVDSALDIIMS platinum vapor deposition surface- m/z mass-to-charge ratio assisted laser desorption/ionization MUC mucin imaging mass spectrometry MW molecular weight Q quadrupole MurNAc N-acetyl muramic acid QIT quadrupole ion trap NBRC Biological Resource Center R- reflectron (as in R-TOF) Nd:Yag neodymium-doped yttrium aluminum rEGCase recombinant endoglycoceramidase II garnet RF radio frequency NEDC N-(1-naphthyl)ethylenediamine Rha rhamnose (6-deoxymannose) dihydrochloride Rib ribose NEDN N-(1-naphthyl)ethylenediamine RNA ribonucleic acid dinitrate RNase ribonuclease Neu5Ac N-acetylneuraminic (sialic) acid RP reversed phase Neu5Gc N-glycoylneuraminic acid rpm revolutions/minute NK natural cancer killing cells SA sinapinic acid NMR nuclear magnetic resonance SALDI surface-assisted laser desorption/ Nod factor nodulation factor ionization NP nanoparticle SAMDI self-Assembled monolayers and NpCCA (E)-2-cyano-3-(naphthalen-2-yl)acrylic matrix-assisted laser desorption acid ionization time-of-flight NPDC1 neuronal differentiation and SAMs sel-assembled monolayers proliferation factor-1 SAP serum amyloid P component OEG oligo(ethylene glycol) sDHB super-DHB (DHB þ 10% 2-hydroxy- OR optical rotation 5-methoxybenzoic acid) ORD optical rotary dispersion SDS sodium dodecyl sulfate OTase oligosaccharyltransferases SEKDEL peptide (Ser-Glu-Lys-Asp-Glu-Leu) p (as in Glcp) pyranose form of sugar ring SELDI surface-enhanced laser desorption/ P (as in GlcP) phosphate ionization PAD pulsed amperometric detection Ser serine PADRE peptide (Pro-Ala-Asp-Arg-Glu) SiaLeC Sialyl LewisC PAGE polyacrylamide gel electrophoresis SIMS secondary ion mass spectrometry PAMAM poly(amidoamine) siRNA small (short) interfering RNA PDAM 1-pyrenyldiazomethane sLeX Sialyl LewisX PDB protein data bank S/N signal-to-noise ratio PE phosphoethanolamine SNA Sambucus nigra agglutinin PEG polyethylene glycol SPE solid-phase extraction PMP 1-phenyl-3-methyl-5-pyrazolone SREC-1 scavenger receptor expressed in PIAT peptide immobilized pH gradient endothelial cells isoelectric focusing assisted TiO2 SRM selected reaction monitoring chromatography STOF spiralTOF PIM phosphatidyl-myo-inositol mannosides -T (as GlcNAc-T) transferase PMAA partially methylated alditols acetates TB tuberculosis PMP 1-phenyl-3-methyl-5-pyrazolone TFA trifluoroacetic acid PNA peptide nucleic acids THAP trihydroxyacetophenone PNGase protein-N-glycosidase TIMP tissue inhibitor of metalloproteinase PQD pulsed-Q dissociation TIPDS tetraisopropyldisilylene Pro proline TLC thin-layer chromatography PSA porcine serum albumin TLR2 toll-like receptor 2 PSD post-source decay Thr threonine Pse pseudaminic acid TOF time-of-flight Pse5Ac7Ac 5,7-diacetamido-3,5,7,9-tetradeoxy-L- TROC 2,2,2-trichlororthoxycarbonyl glycero-L-manno-nonulosonic acid UDP uridine diphosph(ate)(o) Pse5Am7Ac 5-acetamidino-7-acetamido-3,5,7,9- UV ultraviolet tetradeoxy-L-glycero-L-manno- UVDP ultra violet photodissociation nonulosonic acid WGA wheat germ agglutinin PTFE polytetrafluoroethylene XG xyloglycans PUGNAc O-(2-acetamid-O-2-deoxy-D- XOS xylooligosaccharides glucopyranosylidene)amino-N- Xyl xylose phenylcarbamate XylT xylosyltransferase PVDF polyvinylidine difluoride ZFL zebra fish liver

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REFERENCES delivery in senescent cells using capped mesoporous silica nanoparticles. Angew Chem Int Ed 51:10556–10560. Aachary AA, Prapulla SG. 2011. Xylooligosaccharides (XOS) as an Ahn M, Sohn H, Nan YH, Murugan RN, Cheong C, Ryu EK, Kim E-H, emerging prebiotic: Microbial synthesis, utilization, structural charac- Kang SW, Kim EJ, Shin SY, Bang JK. 2011a. Functional and structural terization, bioactive properties, and applications. Comp Rev Food Sci characterization of drosocin and its derivatives linked O-GalNAc at Food Safety 10:2–16. Thr11 residue. Bull Korean Chem Soc 32:3327–3332. Abdel-Aal A-BM, El-Naggar D, Zaman M, Batzloff M, Toth I. 2012. Design Ahn M, Murugan RN, Nan YH, Cheong C, Sohn H, Kim E-H, Hwang E, of fully synthetic, self-adjuvanting vaccine incorporating the tumor- Ryu EK, Kang SW, Shin SY, Bang JK. 2011b. Substitution of the associated carbohydrate Tn antigen and lipoamino acid-based toll-like GalNAc-a-O-Thr11 residue in drosocin with O-linked glyco-peptoid receptor 2 ligand. J Med Biochem 55:6968–6974. residue: Effect on antibacterial activity and conformational change. Abe M, Shimaoka H, Fukushima M, Nishimura S-I. 2012a. A cross-linked Bioorg Med Chem Lett 21:6148–6153. polymer possessing a high density of hydrazide groups: High- Ahn M, Murugan RN, Shin SY, Kim E, Lee JH, Kim HJ, Bang JK. 2012a. throughput glycan purification and labeling for high-performance Synthesis of cyclic antifreeze glycopeptide and glycopeptoids and their liquid chromatography analysis. Polym J 44:269–277. ice recrystallization inhibition activity. Bull Korean Chem Soc Abe T, Horiuchi K, Kikuchi H, Aritsuka T, Takata Y, Fukushi E, Fukushi Y, 33:3565–3570. Kawabata J, Ueno K, Onodera S, Shiomi N. 2012b. Structural Ahn M, Murugan RN, Kim E, Lee JH, Cheong C, Kang SW, Park HJ, Shin confirmation of oligosaccharides newly isolated from sugar beet SY, Kim HJ, Bang JK. 2012b. Studies on the effect of number of sugar molasses. Chem Cent J 6. Article 89. moiety in the antifreeze activity of homodimeric AFGPs. Bull Korean Achelle S, Couleaud P, Baldeck P, Teulade-Fichou M-P, Maillard P. 2011. Chem Soc 33:2411–2414. Carbohydrate-porphyrin conjugates with two-photon absorption prop- Aich U, Beckley N, Shriver Z, Raman R, Viswanathan K, Hobbie S, erties as potential photosensitizing agents for photodynamic therapy. Sasisekharan R. 2011. Glycomics-based analysis of chicken red blood Eur J Org Chem 1271–1279. cells provides insight into the selectivity of the viral agglutination Acosta DM, Soprano LL, Ferrero MR, Esteva MI, Riarte A, Couto AS, assay. FEBS J 278:1699–1712. Duschak VG. 2012. Structural and immunological characterization of Aikawa J-i Matsuo I, Ito Y. 2012. In vitro mannose trimming property of sulphatides: Relevance of sulphate moieties in Trypanosoma cruzi human ER a-1,2 mannosidase. Glycoconj J 29:35–45. glycoconjugates. Parasite Immunol 34:499–510. Aissou K, Pfaff A, Giacomelli C, Travelet C, Muller€ AHE, Borsali R. 2011. Adamo R, Tontini M, Brogioni G, Romano MR, Costantini G, Danieli E, Fluorescent vesicles consisting of galactose-based amphiphilic copoly- Proietti D, Berti F, Costantino P. 2011. Synthesis of laminarin mers with a p-conjugated sequence self-assembled in water. Macromol fragments and evaluation of a b-(1,3) glucan hexasaccaride-CRM197 Mol Commun 21:912–916. conjugate as vaccine candidate against Candida albicans. J Carbohydr Aithal A, Sharma A, Joshi S, Raghava GPS, Varshney GC. 2012. A database Chem 30:249–280. of microbial polysaccharide antigens and their antibodies. PLoS One 7: Adamo R, Romano MR, Berti F, Leuzzi R, Tontini M, Danieli E, Cappelletti e34613. E, Cakici OS, Swennen E, Pinto V, Brogioni B, Proietti D, Galeotti CL, Akasaka-Manya K, Manya H, Mizuno M, Inazu T, Endo T. 2011. Effects of Lay L, Monteiro MA, Scarselli M, Costantino P. 2012. Phosphorylation length and amino acid sequence of O-mannosyl peptides on substrate of the synthetic hexasaccharide repeating unit is essential for the specificity of protein O-linked mannose b1,2-N-acetylglucosaminyl- induction of antibodies to Clostridium difficile PSII cell wall polysac- transferase 1 (POMGnT1). Biochem Biophys Res Commun 410:632– charide. ACS Chem Biol 7:1420–1428. 636. ~ Adao CR, da Silva BP, Paz Parente J. 2011a. A new steroidal saponin from Alavi A, Goodfellow L, Fraser O, Tarelli E, Bland M, Axford J. 2011. A Allium ampeloprasum var. porrum with antiinflammatory and gastro- double-blind, randomized, placebo-controlled study to explore the protective effects. Phytochem Lett 4:306–310. efficacy of a dietary plant-derived polysaccharide supplement in Ad~ao CR, da Silva BP, Paz Parente J. 2011b. A new steroidal saponin with patients with rheumatoid arthritis. Rheumatology 50:1111–1119. antiinflammatory and antiulcerogenic properties from the bulbs of Albrecht S, van Muiswinkel GCJ, Xu J, Schols HA, Voragen AGJ, Allium ampeloprasum var. porrum. Fitoterapia 82:1175–1180. Gruppen H. 2011. Enzymatic production and characterization of Ad~ao CR, da Silva BP, Tinoco LW, Paz Parente J. 2012. Haemolytic activity konjac glucomannan oligosaccharides. J Agric Food Chem and immunological adjuvant effect of a new steroidal saponin from 59:12658–12666. Allium ampeloprasum var. porrum. Chem Biodiversity 9:58–67. Aldredge D, An HJ, Tang N, Waddell K, Lebrilla CB. 2012. Annotation of a Adeuya A, Price NPJ. 2012. Enumeration of hydroxyl groups of sugars and serum N-glycan library for rapid identification of structures. J sugar alcohols by aqueous-based acetylation and matrix-assisted laser Proteome Res 11:1958–1968. desorption/ionization time-of-flight mass spectrometry. Rapid Com- Ali Y, Nisar-ur-Rahman, Idrees MA, Mohsin S, Ahmed S, Ahmed I. 2011. mun Mass Spectrom 26:1372–1376. Sustained release of captopril from matrix tablet using methylcellulose Adinolfi M, Capasso D, Di Gaetano S, Iadonisi A, Leone L, Pastore A. 2011. in a new derivative form. Lat Am J Pharm 30:1696–1701. A straightforward synthetic access to symmetrical glycosyl disulfides Alibaud L, Rombouts Y, Trivelli X, Burguiere A, Cirillo SLG, Cirillo JD, and biological evaluation thereof. Org Biomol Chem 9:6278–6283. Dubremetz J-F, Guerardel Y, Lutfalla G, Kremer L. 2011. A Adinolfi M, d’Ischia M, Iadonisi A, Leone L, Pezzella A, Valerio S. 2012. Mycobacterium marinum TesA mutant defective for major cell wall- Glycosylated eumelanin building blocks by thioglycosylation of 5,6- associated lipids is highly attenuated in Dictyostelium discoideum and diacetoxyindole with an expedient selenium-based dynamic-mixture zebrafish embryos. Mol Microbiol 80:919–934. methodology. Eur J Org Chem 4333–4338. Aljabali AAA, Barclay JE, Cespedes O, Rashid A, Staniland SS, Lomonoss- Adlercreutz D, Yoshimura Y, Mannerstedt K, Wakarchuk WW, Bennett EP, off GP, Evans DJ. 2011. Charge modified cowpea mosaic virus Dovichi NJ, Hindsgaul O, Palcic MM. 2012. Thiogalactopyranosides particles for templated mineralization. Adv Funct Mater 21:4137– are resistant to hydrolysis by a-galactosidases. ChemBioChem 4142. 13:1673–1679. Alley WRJ, Vasseur JA, Goetz JA, Svoboda M, Mann BF, Matei DE, Aggarwal A, Singh S, Zhang Y, Anthes M, Samaroo D, Gao R, Drain CM. Menning N, Hussein A, Mechref Y, Novotny MV. 2012. N-Linked 2011. Synthesis and photophysics of an octathioglycosylated zinc(II) glycan structures and their expressions change in the blood sera of phthalocyanine. Tetrahedron Lett 52:5456–5459. ovarian cancer patient. J Proteome Res 11:2282–2300. Agostini A, Mondragon L, Bernardos A, Martnez-Manez~ R, Marcos MD, Altunkeyik H, Gulcemal€ D, Masullo M, Alankus-Caliskan O, Piacente S, Sancenon F, Soto J, Costero A, Manguan-Garca C, Perona R, Moreno- Karayildirim T. 2012. Triterpene saponins from Cyclamen hederifo- Torres M, Aparicio-Sanchis R, Murgua JR. 2012. Targeted cargo lium. Phytochem Lett 73:127–133.

Mass Spectrometry Reviews DOI 10.1002/mas 121 & HARVEY

Alwael H, Connolly D, Clarke P, Thompson R, Twamley B, O’Connor B, Angel PM, Spraggins JM, Baldwin HS, Caprioli R. 2012. Enhanced Paull B. 2011. Pipette-tip selective extraction of glycoproteins with sensitivity for high spatial resolution lipid analysis by negative ion lectin modified gold nano-particles on a polymer monolithic phase. mode matrix assisted laser desorption ionization imaging mass Analyst 136:2619–2628. spectrometry. Anal Chem 84:1557–1564. Amano M, Hashimoto R, Nishimura S-I. 2012a. Effects of single genetic Angelini R, Corral P, Lopalco P, Ventosa A, Corcelli A. 2012a. Novel ether damage in carbohydrate-recognizing proteins in mouse serum N- lipid cardiolipins in archaeal membranes of extreme haloalkaliphiles. glycan profile revealed by simple glycotyping analysis. ChemBioChem Biochim Biophys Acta 1818:1365–1373. 13:451–464. Angelini R, Vitale R, Patil VA, Cocco T, Ludwig B, Greenberg ML, Corcelli Amano M, Eriksson H, Manning JC, Detjen KM, Andre S, Nishimura S-I, A. 2012b. Lipidomics of intact mitochondria by MALDI-TOF/MS. J Lehtio€ J, Gabius H-J. 2012b. Tumour suppressor p16INK4a—Anoikis- Lipid Res 53:1417–1425. favouring decrease in N/O-glycan/cell surface sialylation by down- Anraku T, Fukuda K, Saito T, Messer M, Urashima T. 2012. Chemical regulation of enzymes in sialic acid biosynthesis in tandem in a characterization of acidic oligosaccharides in milk of the red kangaroo pancreatic carcinoma model. FEBS J 279:4062–4080. (Macropus rufus). Glycoconj J 29:147–156. Amigo-Benavent M, Clemente A, Ferranti P, Caira S, del Castillo MD. 2011. Antonopoulos A, North SJ, Haslam SM, Dell A. 2011. Glycosylation of Digestibility and immunoreactivity of soybean b-conglycinin and its mouse and human immune cells: Insights emerging from N-glycomics deglycosylated form. Food Chem 129:1598–1605. analyses. Biochem Soc Trans 39:1334–1340. Amin MN, Huang W, Mizanur RM, Wang L-X. 2011. Convergent synthesis Antonopoulos A, Demotte N, Stroobant V, Haslam SM, van der Bruggen P, of homogeneous Glc1Man9GlcNAc2-protein and derivatives as ligands Dell A. 2012. Loss of effector function of human cytolytic T of molecular chaperones in protein. J Am Chem Soc 133:14404–14417. lymphocytes is accompanied by major alterations in N- and O- Amore A, Amoresano A, Birolo L, Henrissat B, Leo G, Palmese A, Faraco V. glycosylation. J Biol Chem 287:11240–11251. 2012. A family GH51 a-L-arabinofuranosidase from Pleurotus ostrea- Antonov AS, Avilov SA, Kalinovsky AI, Dmitrenok PS, Kalinin VI, Taboada tus: identification, recombinant expression and characterization. Appl S, Ballesteros M, Avila C. 2011. Triterpene glycosides from Antarctic Microbiol Biotechnol 94:995–1006. sea cucumbers III. Structures of liouvillosides A4 and A5, two minor An HJ, Lebrilla CB. 2011. Structure elucidation of native N- and O-linked disulphated tetraosides containing 3-O-methylquinovose as terminal glycans by tandem mass spectrometry (Tutorial). Mass Spectrom Rev monosaccharide units from the sea cucumber Staurocucumis liouvillei 30:560–578. (Vaney). Nat Prod Res 25:1324–1333. An Y, Cipollo JF. 2011. An unbiased approach for analysis of protein Aranzamendi C, Tefsen B, Jansen M, Chiumiento L, Bruschi F, Kortbeek T, glycosylation and application to influenza vaccine hemagglutinin. Smith DF, Cummings RD, Pinelli E, Van Die I. 2011. Glycan Anal Biochem 415:67–80. microarray profiling of parasite infection sera identifies the LDNF An HJ, Kronewitter SR, De Leoz LA, Peacock KS, Lebrilla CB. 2011. glycan as a potential antigen for serodiagnosis of trichinellosis. Exptl Multi-glycomics platform approach for cancer. J Anal Sci Technol 2: Parasitol 129:221–226. A129–A134. Araujo AC, Nakhai A, Ruda M, Sl€attega˚rd R, Gatenholm P, Brumer H. 2012. Anastyuk SD, Barabanova AO, Correc G, Nazarenko EL, Davydova VN, A general route to xyloglucan-peptide conjugates for the activation of Helbert W, Dmitrenok PS, Yermak IM. 2011. Analysis of structural cellulose surfaces. Carbohydr Res 354:116–120. heterogeneity of k/b-carrageenan oligosaccharides from Tichocarpus Arigi E, Blixt O, Buschard K, Clausen H, Levery SB. 2012. Design of a crinitus by negative-ion ESI and tandem MALDI mass spectrometry. covalently bonded glycosphingolipid microarray. Glycoconj J 29:1– Carbohydr Polym 86:546–554. 12. Anastyuk SD, Shevchenko NM, Dmitrenok PS, Zvyagintseva TN. 2012a. Arroyo LA, Herrera CM, Fernandez L, Hankins JV, Trent MS, Hancock Structural similarities of fucoidans from brown algae Silvetia babingto- REW. 2011. The pmrCAB operon mediates polymyxin resistance in nii and Fucus evanescens, determined by tandem MALDI-TOF mass Acinetobacter baumannii ATCC 17978 and clinical isolates through spectrometry. Carbohydr Res 358:78–81. phosphoethanolamine modification of lipid A. Antimicrob Agents Anastyuk SD, Imbs TI, Shevchenko NM, Dmitrenok PS, Zvyagintseva TN. Chemother 55:3743–3751. 2012b. ESIMS analysis of fucoidan preparations from Costaria Arteaga RG, Pita RCV, Lopez MAL, Labaut JAG, Montero MdC.R. Castro costata, extracted from alga at different life-stages. Carbohydr Polym HV, Alvarez JAC. 2011. Evaluation and evidence of natural ganglio- 90:993–1002. sides with two unsaturated bonds in the ceramide structure obtained by Anastyuk SD, Shevchenko NM, Ermakova SP, Vishchuk OS, Nazarenko EL, a combination of MALDI-MS and NMR spectroscopy. Anal Bioanal Dmitrenok PS, Zvyagintseva TN. 2012c. Anticancer activity in vitro of Chem 400:3675–3680. a fucoidan from the brown alga Fucus evanescens and its low- Artemenko NV, McDonald AG, Davey GP, Rudd PM. 2012. Databases and molecular fragments, structurally characterized by tandem mass- tools in glycobiology. Methods Mol Biol 899:325–350. spectrometry. Carbohydr Polym 87:186–194. Asakawa D, Smargiasso N, De Pauw E. 2012. Identification and relative- Anders N, Wilkinson MD, Lovegrove A, Freeman J, Tryfona T, Pellny TK, quantification of glycans by matrix-assisted laser desorption/ Weimar T, Mortimer JC, Stott K, Baker JM, Defoin-Platel M, Shewry ionization in-source decay with hydrogen abstraction. Anal Chem PR, Dupree P, Mitchell RAC. 2012. Glycosyl transferases in family 61 84:7463–7468. mediate arabinofuranosyl transfer onto xylan in grasses. Proc Natl Asaoka Y, Funazukuri T. 2011. Hydrothermal saccharification of cotton Acad Sci USA 109:989–993. cellulose in dilute aqueous formic acid solution. Res Chem Intermed Andersson P, Jesson G, Kylberg G, Ekstrand G, Thorsen G. 2007. Parallel 37:233–242. nanoliter microfluidic analysis system. Anal Chem 79:4022–4030. Ashour MA-G. 2012. Isolation, HPLC/UV characterization and antioxidant Andersson IE, Andersson CD, Batsalova T, Dzhambazov B, Holmdahl R, activity of phenylethanoids from Blepharis edulis (Forssk.) Pers. Kihlberg J, Linusson A. 2011. Design of glycopeptides used to growing in Egypt. Bull Fac Pharm Cairo Univ 50:67–72. investigate class II MHC binding and T-cell responses associated with Aussedat B, Fasching B, Johnston E, Sane N, Nagorny P, Danishefsky SJ. autoimmune arthritis. PLoS One 6:e17881. 2012. Total synthesis of the a-subunit of human glycoprotein Andrade D, Assis DM, Santos JAN, Alves FM, Hirata IY, Araujo MS, Blaber hormones: Toward fully synthetic homogeneous human follicle- SI, Blaber M, Juliano MA, Juliano L. 2011. Substrate specificity of stimulating hormone. J Am Chem Soc 134:3532–3541. kallikrein-related peptidase 13 activated by salts or glycosaminogly- Bae YJ, Moon JH, Kim MS. 2011. Expansion cooling in the matrix plume is cans and a search for natural substrate candidates. Biochimie 93:1701– under-recognized in MALDI mass spectrometry. J Am Soc Mass 1709. Spectrom 22:1070–1078.

122 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Bae JH, Lim SY. 2012. Chemical composition, antiproliferative and antioxi- Barros MT, Petrova KT, Correia-da-Silva P, Potewara TM. 2011. Library of dant properties of lipid classes in ordinary and dark muscles from chub mild and economic protocols for the selective derivatization of sucrose mackerel (Scomber japonicus). Food Chem Toxicol 50:823–828. under microwave irradiation. Green Chem 13:1897–1906. Bai X, Wang Z, Huang C, Wang Z, Chi L. 2012. Investigation of non- Barta J, Bartova V, Zdrahal Z, S9edo O. 2012. Cultivar variability of patatin enzymatic glycosylation of human serum albumin using ion trap-time biochemical characteristics: Table versus processing potatoes (Sola- of flight mass spectrometry. Molecules 17:8782–8794. num tuberosum L.). J Agric Food Chem 60:4369–4378. Ba€et B, Burel C, Saint-Jean B, Louvet R, Menu-Bouaouiche L, Kiefer- Barthel SR, Antonopoulos A, Cedeno-Laurent F, Schaffer L, Hernandez G, Meyer M-C, Mathieu-Rivet E, Lefebvre T, Castel H, Carlier A, Cadoret Patil SA, North SJ, Dell A, Matta KL, Neelamegham S, Haslam SM, J-P, Lerouge P, Bardor M. 2011. N-Glycans of Phaeodactylum Dimitroff CJ. 2011. Peracetylated 4-fluoro-glucosamine reduces the tricornutum diatom and functional characterization of its N-acetylglu- content and repertoire of N- and O-glycans without direct incorpo- cosaminyltransferase I enzyme. J Biol Chem 286:6152–6164. ration. J Biol Chem 286:21717–21731. Baik JE, Jang K-S, Kang S-S, Yun C-H, Lee K, Kim B-G, Kum K-Y, Han Baruah K, Bowden TA, Krishna BA, Dwek RA, Crispin M, Scanlan CN. SH. 2011. Calcium hydroxide inactivates lipoteichoic acid from 2012. Selective deactivation of serum IgG: A general strategy for the Enterococcus faecalis through deacylation of the lipid moiety. J enhancement of monoclonal antibody receptor interactions. J Mol Biol Endodont 37:191–196. 420:1–7. Bakry R, Rainer M, Huck CW, Bonn GK. 2011. Protein profiling for cancer Barylyuk K, Fritsche L, Balabin RM, Nieckarz R, Zenobi R. 2012. Gas- biomarker discovery using matrix-assisted laser desorption/ionization phase basicity of several common MALDI matrices measured by a time-of-flight mass spectrometry and infrared imaging: A review. Anal simple experimental approach. RSC Adv 2:1962–1969. Chim Acta 690:26–34. Basheer SM, Guiso N, Tirsoaga A, Caroff M, Novikov A. 2011. Structural Balluff B, Schone€ C, Hofler€ H, Walch A. 2011. MALDI imaging mass modifications occurring in lipid A of Bordetella bronchiseptica clinical spectrometry for direct tissue analysis: Technological advancements isolates as demonstrated by matrix-assisted laser desorption/ionization and recent applications. Histochem Cell Biol 136:227–244. time-of-flight mass spectrometry. Rapid Commun Mass Spectrom Ballut S, Naud-Martin D, Loock B, Maillard P. 2011. A strategy for the 25:1075–1081. targeting of photosensitizers. Synthesis, characterization, and photobi- Bastide L, Priem B, Fort S. 2011. Chemo-bacterial synthesis and immunore- ological property of porphyrins bearing glycodendrimeric moieties. J activity of a brain HNK-1 analogue. Carbohydr Res 346:348–351. Org Chem 76:2010–2028. Bateson H, Saleem S, Loadman PM, Sutton CW. 2011. Use of matrix- Balog CIA, Stavenhagen K, Fung WLJ, Koeleman CA, McDonnell LA, assisted laser desorption/ionisation mass spectrometry in cancer Verhoeven A, Mesker WE, Tollenaar RAEM, Deelder AM, Wuhrer M. research. J Pharmacol Toxicol Meth 64:197–206. 2012. N-glycosylation of colorectal cancer tissues. A liquid chroma- Battistel MD, Shangold M, Trinh L, Shiloach J, Freedberg DI. 2012. tography and mass spectrometry-based investigation. Mol Cell Proteo- Evidence for helical structure in a tetramer of a2-8 sialic acid: mics 11:571–585. Unveiling a structural antigen. J Am Chem Soc 134:10717–10720. Balthazar JT, Gusa A, Martin LE, Choudhury B, Carlson R, Shafer WM. Bauer M, Fajolles C, Charitat T, Wacklin H, Daillant J. 2011. Amphiphilic 2011. Lipooligosaccharide structure is an important determinant in the behavior of new cholesteryl cyclodextrins: A molecular study. J Phys resistance of Neisseria gonorrhoeae to antimicrobial agents of innate Chem B 115:15263–15270. host defense. Front Microbiol 2. Article 30. Bauer S. 2012. Mass spectrometry for characterizing plant cell wall Barb AW, Prestegard JH. 2011. NMR analysis demonstrates immunoglobu- polysaccharides. Front Plant Sci 3. Article 45. N lin G -glycans are accessible and dynamic. Nat Chem Biol 7:147– Baumann MJ, Murphy L, Lei N, Krogh KBRM, Borch K, Westh P. 2011. 153. Advantages of isothermal titration calorimetry for xylanase kinetics in Barb AW, Meng L, Gao Z, Johnson RW, Moremen KW, Prestegard JH. 2012. comparison to chemical-reducing-end assays. Anal Biochem 410:19– NMR Characterization of immunoglobulin G Fc glycan motion on 26. enzymatic sialylation. Biochemistry 51:4618–4626. Baycin-Hizal D, Tian Y, Akan I, Jacobson E, Clark D, Chu J, Palter K, Zhang Barboza M, Pinzon J, Wickramasinghe S, Froehlich JW, Moeller I, H, Betenbaugh MJ. 2011a. GlycoFly: A database of Drosophila N- Smilowitz JT, Ruhaak LR, Huang J, Lonnerdal€ B, German B, Medrano linked glycoproteins identified using SPEG-MS techniques. J Prote- JF, Weimer BC, Lebrilla CB. 2012. Glycosylation of human milk ome Res 10:2777–2784. lactoferrin exhibits dynamic changes during early lactation enhancing Baycin-Hizal D, Tian Y, Akan I, Jacobson E, Clark D, Wu A, Jampol R, its role in pathogenic bacteria-host interactions. Mol Cell Proteomics Palter K, Betenbaugh M, Zhang H. 2011b. GlycoFish: A database of 11:M111.015248. zebrafish N-linked glycoproteins identified using SPEG method Barnaby OS, Cerny RL, Clarke W, Hage DS. 2011a. Quantitative analysis of coupled with LC/MS. Anal Chem 83:5296–5303. glycation patterns in human serum albumin using 16O/18O-labeling and Beasley AS, Cotter RJ, Vogel SN, Inzana TJ, Qureshi AA, Qureshi N. 2011. MALDI-TOF MS. Clin Chim Acta 412:1606–1615. A variety of novel lipid A structures obtained from Francisella Barnaby OS, Cerny RL, Clarke W, Hage DS. 2011b. Comparison of tularensis live vaccine strain. Innate Immun 18:268–278. modification sites formed on human serum albumin at various stages of Beceiro A, Llobet E, Aranda J, Bengoechea JA, Doumith M, Hornsey M, glycation. Clin Chim Acta 412:277–285. Dhanji H, Chart H, Bou G, Livermore DM, Woodford N. 2011. Barone R, Sturiale L, Palmigiano A, Zappia M, Garozzo D. 2012a. Phosphoethanolamine modification of lipid A in colistin-resistant Glycomics of pediatric and adulthood diseases of the central nervous variants of Acinetobacter baumannii mediated by the pmrAB two- system. J Proteomics 75:5123–5139. component regulatory system. Antimicrob Agents Chemother 55: Barone R, Aiello C, Race V, Morava E, Foulquier F, Riemersma M, 3370–3379. Passarelli C, Concolino D, Carella M, Santorelli F, Vleugels W, Beck A, Sanglier-Cianferani S, Van Dorsselaer A. 2012. Biosimilar, Mercuri E, Garozzo D, Sturiale L, Messina S, Jaeken J, Fiumara A, biobetter, and next generation antibody characterization by mass Wevers RA, Bertini E, Matthijs G, Lefeber DJ. 2012b. DPM2-CDG: A spectrometry. Anal Chem 84:4637–4646. muscular dystrophy-dystroglycanopathy syndrome with severe epilep- Beckmann HSG, Moller€ HM, Wittmann V. 2012. High-affinity multivalent sy. Ann Neurol 72:550–558. wheat germ agglutinin ligands by one-pot click reaction. Beilstein J Barreteau H, Richard E, Drouillard S, Samain E, Priem B. 2012. Production Org Chem 8:819–826. of intracellular heparosan and derived oligosaccharides by lyase Bedini E, Cirillo L, Parrilli M. 2012. Synthesis of the trisaccharide outer core E. coli expression in metabolically engineered K-12. Carbohydr Res fragment of Burkholderia cepacia pv. vietnamiensis lipooligosacchar- 360:19–24. ide. Carbohydr Res 349:24–32.

Mass Spectrometry Reviews DOI 10.1002/mas 123 & HARVEY

Bekesova S, Kosti O, Chandler KB, Wu J, Madej HL, Brown KC, Simonyan biological activity of recombinant human alpha1-antitrypsin expressed V, Goldman R. 2012. N-glycans in liver-secreted and immunoglogulin- in a novel human neuronal cell line. Biotechnol Bioeng 108:2118– derived protein fractions. J Proteomics 75:2216–2224. 2128. Bello C, Bello GD, Cea M, Nahimana A, Aubry D, Garuti A, Motta G, Blank D, Gebhardt S, Maass K, Lochnit G, Dotz V, Blank J, Geyer R, Kunz Moran E, Fruscione F, Pronzato P, Grossi F, Patrone F, Ballestrero A, C. 2011. High-throughput mass finger printing and Lewis blood group Dupuis M, Sordat B, Zimmermann K, Loretan J, Wartmann M, assignment of human milk oligosaccharides. Anal Bioanal Chem Duchosal MA, Nencioni A, Vogel P. 2011. Anti-cancer activity of 5-O- 401:2495–2510. alkyl-1,4-imino-1,4-dideoxyribitols. Bioorg Med Chem 19:7720–7727. Blank D, Dotz V, Geyer R, Kunz C. 2012a. Human milk oligosaccharides Beloqui A, Sanchez-Ruiz A, Martin-Lomas M, Reichardt N-C. 2012. A and Lewis blood group: Individual high-throughput sample profiling to surface-based mass spectrometry method for screening glycosidase enhance conclusions from functional studies. Adv Nutr 3:440S–449S. specificity in environmental samples. Chem Commun 48:1701–1703. Blank D, Geyer H, Maass K, Yamashita K, Geyer R. 2012b. Elucidation of a Benachour A, Ladjouzi R, Le Jeune A, Hebert L, Thorpe S, Courtin P, novel lacto-N-decaose core structure in human milk using nonlinear Chapot-Chartier M-P, Prajsnar TK, Foster SJ, Mesnagee S. 2012. The analytical technique combinations. Anal Biochem 421:680–690. lysozyme-induced peptidoglycan N-acetylglucosamine deacetylase Blaukopf M, Muller€ B, Hofinger A, Kosma P. 2012. Synthesis of neo- PgdA (EF1843) is required for Enterococcus faecalis virulence. J glycoconjugates containing 4-amino-4-deoxy-L-arabinose epitopes Bacteriol 194:6066–6073. corresponding to the inner core of Burkholderia and Proteus lip- Benediktsdottir BE, Sørensen KK, Thygesen MB, Jensen KJ, Gudjonsson T, opolysaccharides. Eur J Org Chem 119–131. Baldursson O, Masson M. 2012. Regioselective fluorescent labeling of Blixt O, Bueti D, Burford B, Allen D, Julien S, Hollingsworth M, Gammer- N,N,N-trimethyl chitosan via oxime formation. Carbohydr Polym man A, Fentiman I, Taylor-Papadimitriou J, Burchell JM. 2011. 90:1273–1280. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast Benet T, Austin S. 2011. On-line cleanup for 2-aminobenzamide-labeled cancer are associated with a better prognosis. Breast Cancer Res 13. oligosaccharides. Anal Biochem 414:166–168. Article R25. Bennevault-Celton V, Urbach A, Martin O, Pichon C, Guegan P, Midoux P. Blomme B, Van Steenkiste C, Grassi P, Haslam SM, Dell A, Callewaert N, 2011. Supramolecular assemblies of histidinylated a-cyclodextrin in Van Vlierberghe H. 2011. Alterations of serum protein N-glycosylation the presence of DNA scaffold during CDplexes formation. Bioconj in two mouse models of chronic liver disease are hepatocyte and not B Chem 22:2404–2414. cell driven. Am J Physiol Gastrointest Liver Physiol 300:G833–G842. Benoit M, Rodrigues A, Zhang Q, Fourre E, Vigier KDeO, Tatiboue¨t J-M, Bocker€ S, Kehr B, Rasche F. 2011. Determination of glycan structure from Jerome^ F. 2011. Depolymerization of cellulose assisted by a nonther- tandem mass spectra. IEEE/ACM Trans Comput Biol Bioinform mal atmospheric plasma. Angew Chem Int Ed 123:9126–9129. 8:976–986. Bergfeld AK, Pearce OMT, Diaz SL, Lawrence R, Vocadlo DJ, Choudhury Boettcher S, Matwiejuk M, Thiem J. 2012. Acceptor-influenced and donor- B, Esko JD, Varki A. 2012. Metabolism of vertebrate amino sugars tuned base-promoted glycosylation. Beilstein J Org Chem 8:413–420. with N-glycolyl groups. Incorporation of N-glycoylhexosamines into Bøhle LA, Mathiesen G, Vaaje-Kolstad G, Eijsink VGH. 2011. An endo-b- mammalian glycans by feeding N-glycoylgalactosamines. J Biol Chem N-acetylglucosaminidase from Enterococcus faecalisV583 responsible 287:28898–28916. for the hydrolysis of high-mannose and hybrid-type N-linked glycans. Bernard E, Rolain T, Courtin P, Guillot A, Langella P, Hols P, Chapot- FEMS Microbiol Lett 325:123–129. Chartier M-P. 2011. Characterization of O-acetylation of N-acetylglu- Bohme€ J, Anderegg U, Nimptsch A, Nimptsch K, Hacker M, Schulz- cosamine: A novel structural variation of bacterial peptidoglycan. J Siegmund M, Huster D, Schiller J. 2012. De novo biosynthesis of Biol Chem 286:23950–23958. glycosaminoglycans in the extracellular matrix of skin studied by Bernon C, Carre Y, Kuokkanen E, Slomianny M-C, Mir A-M, Krzewinski F, matrix-assisted laser desorption/ionization mass spectrometry. Anal Cacan R, Heikinheimo P, Morelle W, Michalski J-C, Foulquier F, Biochem 421:791–793. Duvet S. 2011. Overexpression of Man2C1 leads to protein under- BojarovaP,SlamovaK,Krenek K, Gazak R, Kulik N, Ettrich R, Pelantova glycosylation and upregulation of endoplasmic reticulum-associated H, Kuzma M, Riva S, Adamek D, Bezouska K, Krena V. 2011. Charged degradation pathway. Glycobiology 21:363–375. hexosaminides as new substrates for b-N-acetylhexosaminidase-cata- Betz J, Bielaszewska M, Thies A, Humpf H-U, Dreisewerd K, Karch H, Kim lyzed synthesis of immunomodulatory disaccharides. Adv Synth Catal € KS, Friedrich AW, Muthing J. 2011. Shiga toxin glycosphingolipid 353:2409–2420. receptors in microvascular and macrovascular endothelial cells: differential association with membrane lipid raft microdomains. J Bokare AD, Choi W. 2011. Advanced oxidation process based on the Cr(III)/ Lipid Res 52:618–634. Cr(VI) redox cycle. Environ Sci Technol 45:9332–9338. Bhamidi S, Scherman MS, Jones V, Crick DC, Belisle JT, Brennan PJ, Bokiej M, Livermore AT, Harris AW, Onishi AC, Sandwick RK. 2011. McNeil MR. 2011. Detailed structural and quantitative analysis reveals Ribose sugars generate internal glycation cross-links in horse heart the spatial organization of the cell walls of in vivo grown Mycobacteri- myoglobin. Biochem Biophys Res Commun 407:191–196. um leprae and in vitro grown Mycobacterium tuberculosis. J Biol Boltje TJ, Kim J-H, Park J, Boons G-J. 2011. Stereoelectronic effects Chem 286:23168–23177. determine oxacarbenium vs b-sulfonium ion mediated glycosylations. Bhat AH, Mondal H, Chauhan JS, Raghava GPS, Methi A, Rao A. 2012. Org Lett 13:284–287. ProGlycProt: a repository of experimentally characterized prokaryotic Boltje TJ, Zhong W, Park J, Wolfert MA, Chen W, Boons G-J. 2012. Chemical glycoproteins. Nucleic Acids Res 40:D388–D393. synthesis and immunological evaluation of the inner core oligosaccharide Bicker KL, Sun J, Lavigne JJ, Thompson PR. 2011. Boronic acid of Francisella tularensis. J Am Chem Soc 134:14255–14262. functionalized peptidyl synthetic lectins: Combinatorial library design, Bond AE, Row PE, Dudley E. 2011a. Post-translation modification of peptide sequencing, and selective glycoprotein recognition. ACS proteins; methodologies and applications in plant sciences. Phyto- Comb Sci 13:232–243. chemistry 72:975–996. Blanchard V, Kaup M, Eigel S, Rieck S, Sandig V, Marx U, Tauber R, Berger Bond MR, Zhang H, Kim J, Yu S-H, Yang F, Patrie SM, Kohler JJ. 2011b. M. 2011a. Quantitative MALDI-TOF-MS using stable-isotope label- Metabolism of diazirine-modified N-acetylmannosamine analogues to ing: Application to the analysis of N-glycans of recombinant a-1 photo-cross-linking sialosides. Bioconj Chem 22:1811–1823. antitrypsin produced using different culture parameters. J Carbohydr Bonomelli C, Doores KJ, Dunlop DC, Thaney V, Dwek RA, Burton DR, Chem 30:320–333. Crispin M, Scanlan CN. 2011. The glycan shield of HIV is predomi- Blanchard V, Liu X, Eigel S, Kaup M, Rieck S, Janciauskiene S, Sandig V, nantly oligomannose independently of production system or viral Marx U, Walden P, Tauber R, Berger M. 2011b. N-Glycosylation and clade. PLoS One 6:e23521.

124 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Boonyapranai K, Tsai H-Y, Chen MC-M, Sriyam S, Sinchaikul S, Phutrakul Broghammer A, Krusell L, Blaise M, Sauer J, Sullivan JT, Maolanon N, S, Chen S-T. 2011. Glycoproteomic analysis and molecular modeling Vinther M, Lorentzen A, Madsen EB, Jensen KJ, Roepstorff P, Thirup of haptoglobin multimers. Electrophoresis 32:1422–1432. S, Ronson CW, Thygesen MB, Stougaard J. 2012. Legume receptors Borbas A, Herczegh P. 2011. Synthesis of lipid II phosphonate analogues. perceive the rhizobial lipochitin oligosaccharide signal molecules by Carbohydr Res 346:1628–1632. direct binding. Proc Natl Acad Sci USA 109:13859–13864. Bordiga M, Travaglia F, Meyrand M, German JB, Lebrilla CB, Co€sson JD, Brown D, Wightman R, Zhang Z, Gomez LD, Atanassov I, Bukowski J-P, Arlorio M, Barile D. 2012. Identification and characterization of Tryfona T, McQueen-Mason SJ, Dupree P, Turner S. 2011a. Arabidop- complex bioactive oligosaccharides in white and red wine by a sis genes IRREGULAR XYLEM (IRX15) and IRX15L encode DUF579- combination of mass spectrometry and gas chromatography. J Agric containing proteins that are essential for normal xylan deposition in the Food Chem 60:3700–3707. secondary cell wall. Plant J 66:401–413. Borlido L, Azevedo AM, Sousa AG, Oliveira PH, Roque ACA, Aires-Barros Brown DB, Huang Y-C, Kannenberg EL, Sherrier DJ, Carlson RW. 2011b. MR. 2012. Fishing human monoclonal antibodies from a CHO cell An acpXL mutant of Rhizobium leguminosarum bv. phaseoli lacks 27- supernatant with boronic acid magnetic particles. J Chrom B 903:163– hydroxyoctacosanoic acid in its lipid A and is developmentally delayed 170. during symbiotic infection of the determinate nodulating host plant Phaseolus vulgaris. J Bacteriol 193:4766–4778. Borromei C, Careri M, Cavazza A, Corradini C, Elviri L, Mangia A, Merusi C. 2011. Evaluation of fructooligosaccharides and inulins as potential- Brown CD, Rusek MS, Kiessling LL. 2012a. Fluorosugar chain termination ly health benefitting food ingredients by HPAEC-PED and MALDI- agents as probes of the sequence specificity of a carbohydrate TOF MS. In: Trimm HH, editor. Analytical chemistry: Methods and polymerase. J Am Chem Soc 134:6552–6555. applications. Oakville, ON: Apple Academic Press. pp. 307–326. Brown DB, Forsberg LS, Kannenberg EL, Carlson RW. 2012b. Characteriza- Børud B, Viburiene R, Hartley MD, Paulsen BS, Egge-Jacobsen W, Imperiali tion of galacturonosyl transferase genes rgtA, rgtB, rgtC, rgtD, and B, Koomey M. 2011. Genetic and molecular analyses reveal an rgtE responsible for lipopolysaccharide synthesis in nitrogen-fixing evolutionary trajectory for glycan synthesis in a bacterial protein endosymbiont Rhizobium leguminosarum. Lipopolysaccharide core glycosylation system. Proc Natl Acad Sci USA 108:9643–9648. and lipid galacturonosyl residues confer membrane stability. J Biol Bossu I, Sulc M, Krenek K, Dufour E, Garcia J, Berthet N, Dumy P, Kren V, Chem 287:935–949. Renaudet O. 2011. Dendri-RAFTs: A second generation of cyclo- Bruel L, Sulzenbacher G, Tison MC, Pujol A, Nicoletti C, Perrier J, Galinier peptide-based glycoclusters. Org Biomol Chem 9:1948–1959. A, Ropartz D, Fons M, Pompeo F, Giardina T. 2011. a-Galactosidase/ Both P, Sobczak L, Breton C, Hann S, Nobauer€ K, Paschinger K, Kozmon S, sucrose kinase (AgaSK), a novel bifunctional enzyme from the human microbiome coupling galactosidase and kinase activities. J Biol Chem Mucha J, Wilson IBH. 2011. Distantly related plant and nematode core a1,3-fucosyltransferases display similar trends in structure-function 286:40814–40823. relationships. Glycobiology 21:1401–1415. Buckow R, Wendorff J, Hemar Y. 2011. Conjugation of bovine serum Bottger€ A, Doxey AC, Hess MW, Pfaller K, Salvenmoser W, Deutzmann R, albumin and glucose under combined high pressure and heat. J Agric Geissner A, Pauly B, Altst€atter J, Munder€ S, Heim A, Gabius H-J, Food Chem 59:3915–3923. McConkey BJ, David CN. 2012. Horizontal gene transfer contributed Bui NK, Turk S, Buckenmaier S, Stevenson-Jones F, Zeuch B, Gobec S, to the evolution of extracellular surface structures: The freshwater Vollmer W. 2011. Development of screening assays and discovery of polyp hydra is covered by a complex fibrous cuticle containing initial inhibitors of pneumococcal peptidoglycan deacetylase PgdA. glycosaminoglycans and proteins of the PPOD and SWT (sweet tooth) Biochem Pharmacol 82:43–52. families. PLoS One 7:e52278. Bui NK, Eberhardt A, Vollmer D, Kern T, Bougault C, Tomasz A, Simorre Boumediene A, Oblet C, Oruc Z, Duchez S, Morelle W, Huynh A, Pourrat J, J-P, Vollmer W. 2012. Isolation and analysis of cell wall components Aldigier J-C, Cogne M. 2011. Gammopathy with IgA mesangial from Streptococcus pneumoniae. Anal Biochem 421:657–666. deposition provides a monoclonal model of IgA nephritogenicity and Bund T, Allelein S, Arunkumar A, Lucey JA, Etzel MR. 2012. Chro- offers new insights into its molecular mechanisms. Nephrol Dial matographic purification and characterization of whey protein-dextran Transplant 26:3930–3937. glycation products. J Chromatogr A 1244:98–105. Boutureira O, Bernardes GJL, D’Hooge F, Davis BG. 2011. Direct radio- Bure C, Cacas J-L, Wang F, Gaudin K, Domergue F, Mongrand S, Schmitter labelling of proteins at cysteine using [18F]-fluorosugars. Chem J-M. 2011. Fast screening of highly glycosylated plant sphingolipids Commun 47:10010–10012. by tandem mass spectrometry. Rapid Commun Mass Spectrom Bowden TA, Baruah K, Coles CH, Harvey DJ, Yu X, Song B-D, Stuart DI, 25:3131–3145. Aricescu R, Scanlan CN, Jones EY, Crispin M. 2012. Chemical and Burgula S, Swarts BM, Guo Z. 2012. Total synthesis of a glycosylphospha- structural analysis of an antibody folding intermediate trapped during tidylinositol anchor of the human lymphocyte CD52 antigen. Chem glycan biosynthesis. J Am Chem Soc 134:17554–17563. Eur J 18:1194–1201. Brandhuber F, Zengerle M, Porwol L, Tenberken O, Thiermann H, Worek F, Burnham-Marusich AR, Snodgrass CJ, Johnson AM, Kiyoshi CM, Buzby Kubik S, Reiter G. 2012. Detoxification of tabun at physiological pH SE, Gruner MR, Berninsone PM. 2012. Metabolic labeling of mediated by substituted b-cyclodextrin and glucose derivatives Caenorhabditis elegans primary embryonic cells with azido-sugars as containing oxime groups. Toxicology 302:163–171. a tool for glycoprotein discovery. PLoS One 7:e49020. Breloy I. 2012. O-Glycomics: Profiling and structural analysis of mucin-type Bushkin GG, Motari E, Magnelli P, Gubbels M-J, Dubey JP, Miska KB, O-linked glycans. Methods Mol Biol 842:165–177. Bullitt E, Costello CE, Robbins PW, Samuelsona J. 2012. b-1,3- Breloy I, Pacharra S, Aust C, Hanisch F-G. 2012a. A sensitive gel-based Glucan, which can be targeted by drugs, forms a trabecular scaffold in global O-glycomics approach reveals high levels of mannosyl glycans the oocyst walls of Toxoplasma and Eimeria. mBio 3:e00258–e00212. in the high mass region of the mouse brain proteome. Biol Chem Bychowska A, Theilacker C, Czerwicka M, Marszewska K, Huebner J, Holst 393:709–717. O, Stepnowski P, Kaczynski Z. 2011. Chemical structure of wall Breloy I, Pacharra S, Ottis P, Bonar D, Grahn A, Hanisch F-G. 2012b. O- teichoic acid isolated from Enterococcus faecium strain U0317. Linked N,N’-diacetyllactosamine (LacdiNAc)-modified glycans in Carbohydr Res 346:2816–2819. extracellular matrix glycoproteins are specifically phosphorylated at Cacciarini M, Nielsen MB, de Castro EM, Marinescu L, Bols M. 2012. b- subterminal N-acetylglucosamine. J Biol Chem 287:18275–18286. Cyclodextrin as a mimetic of the natural GFP-chromophore environ- Broach B, Gu X, Bar-Peled M. 2012. Biosynthesis of UDP-glucuronic acid ment. Tetrahedron Lett 53:973–976. and UDP-galacturonic acid in Bacillus cereus subsp. cytotoxis NVH Cai H, Huang Z-H, Shi L, Zhao Y-F, Kunz H, Li Y-M. 2011a. Towards a fully 391-98. FEBS J 279:100–112. synthetic MUC1-based anticancer vaccine: Efficient conjugation of

Mass Spectrometry Reviews DOI 10.1002/mas 125 & HARVEY

glycopeptides with mono-, di-, and tetravalent lipopeptides using click Casabuono AC, van der Ploeg CA, Roge AD, Bruno SB, Couto AS. 2012. chemistry. Chem Eur J 17:6396–6406. Characterization of lipid A profiles from Shigella flexneri variant X Cai H, Huang Z-H, Shi L, Zou P, Zhao Y-F, Kunz H, Li Y-M. 2011b. lipopolysaccharide. Rapid Commun Mass Spectrom 26:2011–2020. Synthesis of Tn/T antigen MUC1 glycopeptide BSA conjugates and Casas-Solvas JM, Quesada-Soriano I, Carreno-G~ azquez D, Gimenez- their evaluation as vaccines. Eur J Org Chem 3685–3689. Martnez JJ, Garca-Fuentes L, Vargas-Berenguel A. 2011. b-Cyclodex- Cai L, Ban L, Guan W, Mrksich M, Wang PG. 2011c. Enzymatic synthesis trin dimers linked through their secondary faces with rigid spacer arms and properties of uridine-5’-O-(2-thiodiphospho)-N-acetylglucos- as hosts for bile salts. Langmuir 27:9729–9737. amine. Carbohydr Res 346:1576–1580. Caslavska J, Joneli J, Wanzenried U, Schiess J, Thormann W. 2012. Cai H, Huang Z-H, Lei S, Sun Z-Y, Zhao Y-F, Kunz H, Li Y-M. 2012. Transferrin immunoextraction for determination of carbohydrate- Variation of the glycosylation pattern in MUC1 glycopeptide BSA deficient transferrin in human serum by capillary zone electrophoresis. vaccines and its influence on the immune response. Angew Chem Int J Sep Sci 35:3521–3528. Ed 51:1719–1723. Castagnini M, Picchianti M, Talluri E, Biagini M, Del Vecchio M, Di Procolo Cala-De Paepe D, Layre E, Giacometti G, Garcia-Alles LF, Mori L, Hanau P, Norais N, Nardi-Dei V, Balducci E. 2012. Arginine-specific mono D, de Libero G, de la Salle H, Puzo G, Gilleron M. 2012. Deciphering ADP-ribosylation In vitro of antimicrobial peptides by ADP-ribosylat- the role of CD1e protein in mycobacterial phosphatidyl-myo-inositol ing toxins. PLoS One 7:e41417. mannosides (PIM) processing for presentation by CD1b to T lympho- Castaneda-G~ omez J, Pereda-Miranda R. 2011. Resin glycosides from the cytes. J Biol Chem 287:31494–31502. herbal drug Jalap (Ipomoea purga). J Nat Prods 74:1148–1153. Caliot E, Dramsi S, Chapot-Chartier M-P, Courtin P, Kulakauskas S, Catala C, Howe KJ, Hucko S, Rose JKC, Thannhauser TW. 2011. Towards Pechoux C, Trieu-Cuot P, Mistou M-Y. 2012. Role of the group B characterization of the glycoproteome of tomato (Solanum lycopersi- antigen of Streptococcus agalactiae: A peptidoglycan-anchored poly- cum) fruit using concanavalin A lectin affinity chromatography and saccharide involved in cell wall biogenesis. PLoS Pathog 8:e1002756. LC-MALDI-MS/MS analysis. Proteomics 11:1530–1544. Campbell C, Gildersleeve J. 2011. Tools for glycomics: Glycan and lectin Cazares LH, Troyer DA, Wang B, Drake RR, Semmes OJ. 2011. MALDI microarrays. In: Wang B, Boons G-J, editors. Carbohydrate recogni- tissue imaging: from biomarker discovery to clinical applications. Anal tion: Biological problems, methods, and applications. Hoboken: John Bioanal Chem 401:17–27. Wiley and Sons. pp. 205–227. Cazet A, Bobowski M, Rombouts Y, Lefebvre J, Steenackers A, Popa I, Campomenosi P, Cinquetti R, Tallarita E, Lindqvist C, Raimondi I, Grassi P, Guerardel Y, Le Bourhis X, Tulasne D, Delannoy P. 2012. The € Nasman J, Dell A, Haslam SM, Taramelli R. 2011. Comparison of the ganglioside GD2 induces the constitutive activation of c-Met in MDA- baculovirus-insect cell and Pichia pastoris heterologous systems for MB-231 breast cancer cells expressing the GD3 synthase. Glycobiology the expression of the human tumor suppressor protein RNASET2. 22:806–816. Biotechnol Appl Biochem 58:39–49. Cecioni S, Oerthel V, Iehl J, Holler M, Goyard D, Praly J-P, Imberty A, Candela T, Maes E, Garenaux E, Rombouts Y, Krzewinski F, Gohar M, Nierengarten J-F, Vidal S. 2011a. Synthesis of dodecavalent fullerene- Guerardel Y. 2011. Environmental and biofilm-dependent changes in a based glycoclusters and evaluation of their binding properties towards Bacillus cereus secondary cell wall polysaccharide. J Biol Chem a bacterial lectin. Chem Eur J 17:3252–3261. 286:31250–31262. Cecioni S, Faure S, Darbost U, Bonnamour I, Parrot-Lopez H, Roy O, Canis K, McKinnon TAJ, Nowak A, Haslam SM, Panico M, Morris HR, Taillefumier C, Wimmerova M, Praly J-P, Imberty A, Vidal S. 2011b. Laffan MA, Dell A. 2012. Mapping the N-glycome of human von Selectivity among two lectins: Probing the effect of topology, multi- Willebrand factor. Biochem J 447:217–228. valency and flexibility of clicked multivalent glycoclusters. Chem Eur Cao W, Cao J, Huang J, Zhang L, Yao J, Xu H, Yang P. 2012. Enhanced N- J 17:2146–2159. glycosylation site exploitation of sialoglycopeptides by peptide IPG- Cerruti CD, Touboul D, Guerineau V, Petit VW. 2011. MALDI imaging IEF assisted TiO2 chromatography. Glycoconj J 29:433–443. mass spectrometry of lipids by adding lithium salts to the matrix Capicciotti CJ, Trant JF, Leclere M, Ben RN. 2011. Synthesis of C-linked solution. Anal Bioanal Chem 401:75–87. triazole-containing AFGP analogues and their ability to inhibit ice Cerruti CD, Benabdellah F, Laprevote O, Touboul D, Brunelle A. 2012. recrystallization. Bioconj Chem 22:605–616. Imaging and structural analysis of rat brain lipid negative ions with 9- Cardote TAF, Barata JFB, Faustino MAF, Preuß A, Neves MGPMS, aminoacridine matrix. Anal Chem 84:2164–2171. Cavaleiro JAS, Ramos CIV, Santana-Marques MGO, Roder€ B. 2012. Cervera-Tison M, Tailford LE, Fuell C, Bruel L, Sulzenbacher G, Henrissat Pentafluorophenylcorrole-D-galactose conjugates. Tetrahedron Lett B, Berrin JG, Fons M, Giardina T, Juge N. 2012. Functional analysis of 53:6388–6393. family GH36 a-galactosidases from Ruminococcus gnavus E1: In- Carillo S, Pieretti G, Parrilli E, Tutino ML, Gemma S, Molteni M, Lanzetta sights into the metabolism of a plant oligosaccharide by a human gut R, Parrilli M, Corsaro MM. 2011. Structural investigation and biological symbiont. Appl Environ Microbiol 78:7720–7732. activity of the lipooligosaccharide from the psychrophilic bacterium Chabre YM, Giguere D, Blanchard B, Rodrigue J, Rocheleau S, Neault M, Pseudoalteromonas haloplanktis TAB 23. Chem Eur J 17:7053–7060. Rauthu S, Papadopoulos A, Arnold AA, Imberty A, Roy R. 2011. Carlsson MC, Balog CIA, Kilsga˚rd O, Hellmark T, Bakoush O, Segelmark Combining glycomimetic and multivalent strategies toward designing M, Ferno€ M, Olsson H, Malmstrom€ J, Wuhrer M, Leffler H. 2012. potent bacterial lectin inhibitors. Chem Eur J 17:6545–6562. Different fractions of human serum glycoproteins bind galectin-1 or Chae PS, Rasmussen SGF, Rana RR, Gotfryd K, Kruse AC, Manglik A, Cho galectin-8, and their ratio may provide a refined biomarker for KH, Nurva S, Gether U, Guan L, Loland CJ, Byrne B, Kobilka BK, pathophysiological conditions in cancer and inflammatory disease. Gellman SH. 2012. A new class of amphiphiles bearing rigid Biochim Biophys Acta 1820:1366–1372. hydrophobic groups for solubilization and stabilization of membrane Caroff M, Novikov A. 2011. Micromethods for lipid A isolation and proteins. Chem Eur J 18:9485–9490. structural characterization. Methods Mol Biol 739:135–146. Chafchaouni-Moussaoui I, Novikov A, Bhrada F, Perry MB, Filali-Maltouf Carulli S, Calvano CD, Palmisano F, Pischetsrieder M. 2011. MALDI-TOF A, Caroff M. 2011. A new rapid and micro-scale hydrolysis, using MS characterization of glycation products of whey proteins in a triethylamine citrate, for lipopolysaccharide characterization by mass glucose/galactose model system and lactose-free milk. J Agric Food spectrometry. Rapid Commun Mass Spectrom 25:2043–2048. Chem 59:1793–1803. Chang Y-L, Lee Y-C, Yang W-B, Chen C-H. 2011a. Ionic liquid-assisted Casabuono A, Petrocelli S, Ottado J, Orellano EG, Couto AS. 2011. electrospray ionization of polysaccharides. J Mass Spectrom 46:367– Structural analysis and involvement in plant innate immunity of 375. Xanthomonas axonopodis pv. citri lipopolysaccharide. J Biol Chem Chang Y-L, Liao SK-S, Chen Y-C, Hung W-T, Yu H-M, Yang W-B, Fang J- 286:25628–25643. M, Chen C-H, Chuan LY. 2011b. Tagging saccharides for signal

126 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

enhancement in mass spectrometric analysis. J Mass Spectrom endemic meningococcal disease recognizes an internal lacto-N-neo- 46:247–255. tetraose structure. J Biol Chem 286:43622–43633. Chantret I, Kodali VP, Lahmouich C, Harvey DJ, Moore SEH. 2011. Cheng S-C, Huang M-Z, Shiea J. 2011b. Thin layer chromatography/mass Endoplasmic reticulum-associated degradation (ERAD) and free spectrometry. J Chromatogr A 1218:2700–2711. oligosaccharide generation in Saccharomyces cerevisiae. J Biol Chem Cheng Q-Y, Zhou D, Gao Y, Chen Q, Zhang Z, Han B-H. 2012. 286:41786–41800. Supramolecular self-assembly induced graphene oxide based hydro- Charkin OP, Klimenko NM, Chen B-G, Lin S-H, Chen C-H. 2011. gels and organogels. Langmiur 28:3005–3010. Theoretical and experimental study of the structure and stability of Chevolot Y. 2012. Carbohydrate microarrays (methods in molecular biology multiply Na-substituted glucose and 2,4,6-trihydroxyacetophenone series, Volume 808). Totowa, NJ, USA: Humana, Springer. derivatives. Russ J Inorg Chem 56:61–70. Childs-Disney JL, Parkesh R, Nakamori M, Thornton CA, Disney MD. Chauhan JS, Bhat AH, Raghava GPS, Rao A. 2012. GlycoPP: A webserver 2012. Rational design of bioactive, modularly assembled aminoglyco- for prediction of N- and O-glycosites in prokaryotic protein sequences. sides targeting the RNA that causes myotonic dystrophy type. ACS PLoS One 7:e40155. Chem Biol 7:1984–1993. Chavadi SS, Onwueme KC, Edupuganti UR, Jerome J, Chatterjee D, Soll Chinthaka SDM, Rodgers MT. 2012. Sodium cation affinities of commonly CE, Quadri LEN. 2012. The mycobacterial acyltransferase PapA5 is used MALDI matrices determined by guided ion beam tandem mass required for biosynthesis of cell wall-associated phenolic glycolipids. spectrometry. J Am Soc Mass Spectrom 23:676–689. Microbiology 158:1379–1387. Cho E, Choi JM, Kim H, Lee I-S, Jung S. 2011. Hydrophobic interactions of Chavaroche AAE, van den Broek LAM, Boeriu C, Eggink G. 2012. succinoglycan dimers isolated from Sinorhizobium meliloti with Synthesis of heparosan oligosaccharides by Pasteurella multocida hydrophobic fluorescence probes, 8-anilino-1-naphthalenesulfonate PmHS2 single-action transferases. Appl Microbiol Biotechnol and 6-p-toluidino-2-naphthalenesulfonate. Bull Korean Chem Soc 95:1199–1210. 32:4071–4074. Chen R, Tolbert TJ. 2011. On-resin convergent synthesis of a glycopeptide Choi JY, Jeong JM, Yoo BC, Kim K, Kim Y, Yang BY, Lee Y-S, Lee DS, from HIV gp120 containing a high mannose N-linked oligosaccharide. Chung J-K, Lee MC. 2011. Development of 68Ga-labeled mannosy- Methods Mol Biol 751:343–355. lated human serum albumin (MSA) as a lymph node imaging agent for Chen W, Gu L, Zhang W, Motari E, Cai L, Styslinger TJ, Wang PG. 2011. positron emission tomography. Nucl Med Biol 38:371–379. L-Rhamnose antigen: A promising alternative to a-Gal for cancer Choi JM, Kim K, Cho E, Jung S. 2012a. Solubility enhancement of salicylic immunotherapies. Chem Biol 6:185–191. acid by complexation with succinoglycan monomers isolated from Chen X, Cao D, Zhou L, Jin H, Dong Q, Yao J, Ding K. 2011b. Structure of a Sinorhizobium meliloti. Bull Korean Chem Soc 33:2091–2094. polysaccharide from Gastrodia elata Bl., and oligosaccharides pre- Choi JM, Kim H, Cho E, Choi Y, Lee IS, Jung S. 2012b. Solubilization of pared thereof with anti-pancreatic cancer cell growth activities. haloperidol by acyclic succinoglycan oligosaccharides. Carbohydr Carbohydr Polym 86:1300–1305. Polym 89:564–570. Chen Y-Y, Peng B, Yang Q, Glew MD, Veith PD, Cross KJ, Goldie KN, Chen D, O’Brien-Simpson N, Dashper SG, Reynolds EC. 2011c. Choi SH, Chung JW, Priestley RD, Kwak S-Y. 2012c. Functionalization of The outer membrane protein LptO is essential for the O-deacylation polysulfone hollow fiber membranes with amphiphilic b-cyclodextrin of LPS and the co-ordinated secretion and attachment of A-LPS and and their applications for the removal of endocrine disrupting plasticiz- CTD proteins in Porphyromonas gingivalis. Mol Microbiol 79:1380– er. J Membrane Sci 409–410:75–81. 1401. Choi SY, Jeong HJ, Lim HG, Park SS, Kim SH, Kim YJ. 2012d. Elimination Chen Y, Sun Z-H, Song B-E, Liu Y. 2011d. Naphthylthiourea-modified of alpha-gal xenoreactive epitope: Alpha-galactosidase treatment of permethylcyclodextrin as a highly sensitive and selective turn-on porcine heart valves. J Heart Valve Dis 21:387–397. fluorescent chemosensor for Hg2þ in water and living cells. Org Choisnard L, Geze A, Vanhaverbeke C, Yameogo JBG, Putaux J-L, Brasme Biomol Chem 9:5530–5534. B, Jullien L, Boullanger S, Elfakir C, Wouessidjewe D. 2011. Chen Y, Cao J, Yan G, Lu H, Yang P. 2011e. Two-step protease digestion Physicochemical characterization of a-, b-, and g-cyclodextrins and glycopeptide capture approach for accurate glycosite identification bioesterified with decanoate chains used as building blocks of colloidal and glycoprotein sequence coverage improvement. Talanta 85: nanoparticles. Biomacromolecules 12:3031–3038. 70–75. Choma A, Komaniecka I. 2011. Characterization of cyclic b-glucans of Chen C, Constantinou A, Chester KA, Vyas B, Canis K, Haslam SM, Dell A, Bradyrhizobium by MALDI-TOF mass spectrometry. Carbohydr Res Epenetos AA, Deonarain MP. 2012a. Glycoengineering approach to 346:1945–1950. half-life extension of recombinant biotherapeutics. Bioconj Chem Choma A, Komaniecka I, Turska-Szewczuk A, Danikiewicz W, Spolnik G. 23:1524–1533. 2012. Structure of lipid A from a stem-nodulating bacterium Azorhi- Chen G, Wang Y, Qiu L, Qin X, Liu H, Wang X, Wang Y, Song G, Li F, Guo zobium caulinodans. Carbohydr Res 352:126–136. Y, Li F, Guo S, Li Z. 2012b. Human IgG Fc-glycosylation profiling Chong S-L, Nissil€a T, Ketola RA, Koutaniemi S, Derba-Maceluch M, reveals associations with age, sex, female sex hormones and thyroid Mellerowicz EJ, Tenkanen M, Tuomainen P. 2011. Feasibility of using cancer. J Proteomics 75:2824–2834. atmospheric pressure matrix-assisted laser desorption/ionization with Chen R, Chen S, Xiong C, Ding X, Wu C-C, Chang H-C, Xiong S, Nie Z. ion trap mass spectrometry in the analysis of acetylated xylooligosac- 2012c. N-(1-Naphthyl) ethylenediamine dinitrate: A new matrix for charides derived from hardwoods and Arabidopsis thaliana. Anal negative ion MALDI-TOF MS analysis of small molecules. J Am Soc Bioanal Chem 401:2995–3009. Mass Spectrom 23:1454–1460. Chougale AD, Bhat SP, Bhujbal SV, Zambare MR, Puntambekar S, Somani Chen R, Xu W, Xiong C, Zhou X, Xiong S, Nie Z, Mao L, Chen Y, Chang H- RS, Boppana R, Giri AP, Kulkarni MJ. 2012. Proteomic analysis of C. 2012d. High-salt-tolerance matrix for facile detection of glucose in glycated proteins from streptozotocin-induced diabetic rat kidney. Mol rat brain microdialysates by MALDI mass spectrometry. Anal Chem Biotechnol 50:28–38. 84:465–469. Chowdhury SR, Basak RK, Sen R, Adhikari B. 2011a. Characterization and Chen S-C, Wu P-H, Su Y-C, Wen T-N, Wei Y-S, Wang N-C, Hsu C-A, Wang emulsifying property of a carbohydrate polymer produced by Bacillus AH-J, Shyur L-F. 2012e. Biochemical characterization of a novel pumilus UW-02 isolated from waste water irrigated agricultural soil. laccase from the basidiomycete fungus Cerrena sp. WR1. Protein Eng Int J Biol Macromol 48:705–712. 25:761–769. Chowdhury SR, Basak RK, Sen R, Adhikaria B. 2011b. Production of Cheng H, Yang Z, Estabrook MM, John CM, Jarvis GA, McLaughlin S, extracellular polysaccharide by Bacillus megaterium RB-05 using jute Griffiss JM. 2011a. Human lipooligosaccharide IGG that prevents as substrate. Bioresource Technol 102:6629–6632.

Mass Spectrometry Reviews DOI 10.1002/mas 127 & HARVEY

Chowdhury SR, Manna S, Saha P, Basak RK, Sen R, Roy D, Adhikari B. lipopolysaccharide core of Brucella abortus acts as a shield against 2011c. Composition analysis and material characterization of an innate immunity recognition. PLoS Pathog 8:e1002675. emulsifying extracellular polysaccharide (EPS) produced by Bacillus Cook KS, Bullock K, Sullivan T. 2012. Development and qualification of an megaterium RB-05: A hydrodynamic sediment attached isolate of antibody rapid deglycosylation method. Biologicals 40:109–117. freshwater origin. J Appl Microbiol 111:1381–1393. Coppola C, Simeone L, De Napoli L, Montesarchio D. 2011. On the Chowdhury S, Mandal C, Sarkar S, Bag AK, Vlasak R, Chandra S, Mandal compatibility of azides in phosphoramidite-based couplings: Synthesis C. 2012. Mobilization of lymphoblasts from bone marrow to peripheral of a novel, convertible azido-functionalized CyPLOS analogue. Eur J blood in childhood acute lymphoblastic leukaemia: Role of 9-O- Org Chem 1155–1165. acetylated sialoglycoproteins. Leukemia Res 36:146–155. Correia MAS, Mazumder K, Bras JLA, Firbank SJ, Zhu Y, Lewis RJ, York Christensen HS, Sigurskjold BW, Frihed TG, Marinescu LG, Pedersen CM, WS, Fontes CMGA, Gilbert HJ. 2011. Structure and function of an Bols M. 2011. Recognition of peptides by cyclodextrin trimers. Eur J arabinoxylan-specific xylanase. J Biol Chem 286:22510–22520. Org Chem 5279–5290. Cortes DF, Kabulski JL, Lazar AC, Lazar IM. 2011. Recent advances in the Chung MJ, Park JK, Park YI. 2012a. Anti-inflammatory effects of low- MS analysis of glycoproteins: Capillary and microfluidic workflows. molecular weight chitosan oligosaccharides in IgE-antigen complex- Electrophoresis 32:14–29. stimulated RBL-2H3 cells and asthma model mice. Int Immunophar- Corzo-Martnez M, Sanchez CC, Moreno FJ, Patino JMR, Villamiel M. 2012. macol 12:453–459. Interfacial and foaming properties of bovine b-lactoglobulin: Galac- Chung P-W, Charmot A, Gazit OM, Katz A. 2012b. Glucan adsorption on tose Maillard conjugates. Food Hydrocolloid 27:438–447. mesoporous carbon nanoparticles: Effect of chain length and internal Cot M, Ray A, Gilleron M, Vercellone A, Larrouy-Maumus G, Armau E, surface. Langmiur 28:15222–15232. Gauthier S, Tiraby G, Puzo G, Nigou J. 2011. Lipoteichoic acid in Ciric J, Oostland J, de Vries JW, Woortman AJJ, Loos K. 2012. Size Streptomyces hygroscopicus: Structural model and immunomodulatory exclusion chromatography with multi detection in combination with activities. PLoS One 6:e26316. matrix-assisted laser desorption ionization-time-of-flight mass spec- Cotella D, Radicke S, Cipriani V, Cavaletto M, Merlin S, Follenzi A, Ravens trometry as a tool for unraveling the mechanism of the enzymatic U, Wettwer E, Santoro C, Sblattero D. 2012. N-glycosylation of the polymerization of polysaccharides. Anal Chem 84:10463–10470. mammalian dipeptidyl aminopeptidase-like protein 10 (DPP10) regu- Claes IJJ, Schoofs G, Regulski K, Courtin P, Chapot-Chartier M-P, Rolain T, lates trafficking and interaction with Kv4 channels. Int J Biochem Cell Hols P, von Ossowski I, Reunanen J, de Vos WM, Palva A, Biol 44:876–885. Vanderleyden J, De Keersmaecker SCJ, Lebeer S. 2012. Genetic and Couto AS, Soprano LL, Landoni M, Pourcelot M, Acosta DM, Bultel L, biochemical characterization of the cell wall hydrolase activity of the Parente J, Ferrero MR, Barbier M, Dussouy C, Esteva MI, Kovensky J, major secreted protein of Lactobacillus rhamnosus GG. PLoS One 7: Duschak VG. 2012. An anionic synthetic sugar containing 6-SO3- e31588. NAcGlc mimics the sulfated cruzipain epitope that plays a central role Clarke BR, Richards MR, Greenfield LK, Hou D, Lowary TL, Whitfield C. in immune recognition. FEBS J 279:3665–3679. 2011. In vitro reconstruction of the chain termination reaction in Cox AD, St. Michael F, Cairns CM, Lacelle S, Filion AL, Neelamegan D, biosynthesis of the Escherichia coli O9a O-polysaccharide. The chain- Wenzel CQ, Horan H, Richards JC. 2011. Investigating the potential of length regulator, WbdD, catalyses the addition of methyl phosphate to conserved inner core oligosaccharide regions of Moraxella catarrhalis the non-reducing terminus of the growing glycan. J Biol Chem lipopolysaccharide as vaccine antigens: Accessibility and functional 286:41391–41401. activity of monoclonal antibodies and glycoconjugate derived sera. Clarke DB, Lloyd AS, Robb P. 2012. Application of liquid chromatography Glycoconj J 28:165–182. coupled to time-of-flight mass spectrometry separation for rapid Croitoru R, van den Broek LAM, Frissen AE, Davidescu CM, Peter F, Boeriu Amanita assessment of toxins in mushrooms. Anal Meth 4:1298–1309. CG. 2011. Lipase catalyzed synthesis of aromatic esters of sugar Clayton R, Hardman J, LaBranche CC, McReynolds KD. 2011. Evaluation alcohols. World Acad Sci Eng Technol 52:484–489. of the synthesis of sialic acid-PAMAM glycodendrimers without the Croitoru R, Fitig̨au F, van den Broek LAM, Frissen AE, Davidescu use of sugar protecting groups, and the anti-HIV-1 properties of these CM, Boeriu CG, Peter F. 2012. Biocatalytic acylation of sugar compounds. Bioconj Chem 22:2186–2197. alcohols by 3-(4-hydroxyphenyl) propionic acid. Proc Biochem Clemente MJ, Tejedor RM, Romero P, Fitremann J, Oriol L. 2012a. Maltose- 47:1894–1902. based gelators having azobenzene as light-sensitive unit. RSC Adv Cruz-Morales S, Castan9eda-Gomez J, Figueroa-Gonzalez G, Mendoza- 2:11419–11431. Garca AD, Lorence A, Pereda-Miranda R. 2012. Mammalian multi- Clemente MJ, Romero P, Serrano JL, Fitremann J, Oriol L. 2012b. drug resistance lipopentasaccharide inhibitors from Ipomoea alba Supramolecular hydrogels based on glycoamphiphiles: Effect of the seeds. J Nat Prods 75:1603–1611. disaccharide polar head. Chem Mater 24:3847–3858. ̊ Csavas M, Majer G, Herczeg M, Remenyik J, Lazar L, Mandi A, Borbas A, Clo E, Kracun SK, Nudelman AS, Jensen KJ, Liljeqvist J-A, Olofsson S, Antus S. 2011. Investigation of glycosylating properties of 1-deoxy-1- Bergstrom€ T, Blixt O. 2012. Characterization of the viral O-glycopepti- ethoxysulfonylhept-2-ulopyranosyl derivatives: Synthesis of a new dome: A novel tool of relevance for vaccine design and serodiagnosis. J sulfonic acid mimetic of the sialyl Lewis X tetrasaccharide. Carbohydr Virol 86:6268–6278. Res 346:1527–1533. Coats SR, Berezow AB, To TT, Jain S, Bainbridge BW, Banani KP, Darveau Cucu T, De Meulenaer B, Kerkaert B, Vandenberghe I, Devreese B. 2012. RP. 2011. The lipid A phosphate position determines differential host MALDI based identification of whey protein derived tryptic marker toll-like receptor 4 responses to phylogenetically related symbiotic and peptides that resist protein glycation. Food Res Int 47:23–30. pathogenic bacteria. Infect Immun 79:203–210. Cukan MC, Hopkins D, Burnina I, Button M, Giaccone E, Houston- Coddeville B, Maes E, Ferrier-Pages C, Guerardel Y. 2011. Glycan profiling Cummings NR, Jiang Y, Li F, Mallem M, Mitchell T, Moore R, Nylen of gel forming mucus layer from the scleractinian symbiotic coral A, Prinz B, Rios S, Sharkey N, Zha D, Hamilton S, Li H, Stadheim TA. Oculina arbuscula. Biomacromolecules 12:2064–2073. 2012. Binding of DC-SIGN to glycoproteins expressed in glycoengi- Colsch B, Jackson SN, Dutta S, Woods AS. 2011. Molecular microscopy of neered Pichia pastoris. J Immunol Meth 386:34–42. brain gangliosides: Illustrating their distribution in hippocampal cell Curtis MA, Percival RS, Devine D, Darveau RP, Coats SR, Rangarajan M, layers. ACS Chem Neurosci 2:213–222. Tarelli E, Marsh PD. 2011. Temperature-dependent modulation of Conde-Alvarez R, Arce-Gorvel V, Iriarte M, Mancek-Keber M, Barquero- Porphyromonas gingivalis lipid A structure and interaction with the Calvo E, Palacios-Chaves L, Chacon-D az C, Chaves-Olarte E, innate host defenses. Infect Immun 79:1187–1193. Martirosyan A, von Bargen K, Grillo M-J, Jerala R, Brandenburg K, da Costa G, Gomes RA, Guerreiro A, Mateus E, Monteiro E, Barroso E, Llobet E, Bengoechea JA, Moreno E, Moriyon I, Gorvel J-P. 2012. The Coelho AV, Freire AP, Cordeiro C. 2011. Beyond genetic factors in

128 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

familial amyloidotic polyneuropathy: Protein glycation and the loss of fibrosis pathogens Burkholderia cepacia complex. Carbohydr Chem fibrinogen’s chaperone activity. PLoS One 6:e24850. 38:13–39. Dai C, Cazares LH, Wang L, Chu Y, Wang SL, Troyer DA, Semmes OJ, de Vries RP, Smit CH, de Bruin E, Rigter A, de Vries E, Cornelissen LAHM, Drake RR, Wang B. 2011. Using boronolectin in MALDI-MS imaging Eggink D, Chung NPY, Moore JP, Sanders RW, Hokke CH, Koopmans for the histological analysis of cancer tissue expressing the sialyl Lewis M, Rottier PJM, de Haan CAM. 2012. Glycan-dependent immunoge- X antigen. Chem Commun 47:10338–10340. nicity of recombinant soluble trimeric hemagglutinin. J Virol Dal Bo AG, Soldi V, Giacomelli FC, Travelet C, Jean B, Pignot-Paintrand I, 86:11735–11744. Borsali R, Fort S. 2012. Self-assembly of amphiphilic glycoconjugates Debeire P, Khoune P, Jeltsch J-M, Phalip V. 2012. Product patterns of into lectin-adhesive nanoparticles. Langmuir 28:1418–1426. a feruloyl esterase from Aspergillus nidulans on large feruloyl-arabino- Daly R, Vaz G, Davies AM, Senge MO, Scanlan EM. 2012. Synthesis and xylo-oligosaccharides from wheat bran. Bioresource Technol 119: biological evaluation of a library of glycoporphyrin compounds. Chem 425–428. Eur J 18:14671–14679. Decroocq C, Rodrguez-Lucena D, Russo V, Barragan TM, Mellet CO, Damerell D, Ceroni A, Maass K, Ranzinger R, Dell A, Haslam SM. 2012. Compain P. 2011. The multivalent effect in glycosidase inhibition: The GlycanBuilder and GlycoWorkbench glycoinformatics tools: Probing the influence of architectural parameters with cyclodextrin- Updates and new developments. Biol Chem 393:1357–1362. based iminosugar click clusters. Chem Eur J 17:13825–13831. Damron FH, Davis MRJ, Withers TR, Ernst RK, Goldberg JB, Yu G, Yu HD. Dee SJ, Bell AT. 2011. A study of the acid-catalyzed hydrolysis of 2011. Vanadate and triclosan synergistically induce alginate production cellulose dissolved in ionic liquids and the factors influencing the by Pseudomonas aeruginosa strain PAO1. Mol Microbiol 81:554–570. dehydration of glucose and the formation of humins. ChemSusChem Dang Y, Li S, Wang W, Wang S, Zou M, Guo Y, Fan J, Du Y, Zhang J. 2011. 4:1166–1173. The effects of chitosan oligosaccharide on the activation of murine Defant A, Mancini I, Torri C, Malferrari D, Fabbri D. 2011. An efficient spleen CD11cþ dendritic cells via toll-like receptor 4. Carbohydr route towards a new branched tetrahydrofurane d-sugar amino acid Polym 83:1075–1081. from a pyrolysis product of cellulose. Amino Acids 40:633–640. Daraghmeh NH, Chowdhry BZ, Leharne SA, Al Omari MM, Badwan AA. Delvolve AM, Woods AS. 2011. Optimization of automated matrix 2011. Chitin. In: Brittain HG, editor. Profiles of drug substances, deposition for biomolecular mapping using a spotter. J Mass Spectrom excipients and related methodology. Amsterdam: Elsevier. pp. 35–102. 46:1046–1050. Das I, Desire J, Manvar D, Baussanne I, Pandey VN, Decout J-L. 2012. A Deng K, George KW, Reindl W, Keasling JD, Adams PD, Lee TS, Singh peptide nucleic acid-aminosugar conjugate targeting transactivation AK, Northen TR. 2012. Encoding substrates with mass tags to resolve response element of HIV-1 RNA genome shows a high bioavailability stereospecific reactions using Nimzyme. Rapid Commun Mass Spec- in human cells and strongly Inhibits Tat-mediated transactivation of trom 26:611–615. HIV-1 transcription. J Med Chem 55:6021–6032. Denger K, Huhn T, Hollemeyer K, Schleheck D, Cook AM. 2012. Daus S, Petzold-Welcke K, Kotteritzsch€ M, Baumgaertel A, Schubert US, Sulfoquinovose degraded by pure cultures of bacteria with release of Heinze T. 2011. Homogeneous sulfation of xylan from different C3-organosulfonates: Complete degradation in two-member communi- sources. Macromol Mater and Eng 296:551–561. ties. FEMS Microbiol Lett 328:39–45. Davis SJ, Crispin M. 2011. Solutions to the glycosylation problem for Depetris RS, Julien J-P, Khayat R, Lee JH, Pejchal R, Katpally U, Cocco N, low- and high-throughput structural glycoproteomics. In: Owens RJ, Kachare M, Massi E, David KB, Cupo A, Marozsan AJ, Olson WC, Nettleship JE, editors. Functional and structural proteomics of Ward AB, Wilson IA, Sanders RW, Moore JP. 2012. Partial enzymatic glycoproteins. Dordrecht, Heidelberg, London, New York: Springer. deglycosylation preserves the structure of cleaved recombinant HIV-1 pp. 103–125. envelope glycoprotein trimers. J Biol Chem 287:24239–24254. Davis RA, Lin C-H, Gervay-Hague J. 2012. Chemoenzymatic synthesis of Desantos-Garcia JL, Khalil SI, Hussein A, Hu Y, Mechref Y. 2011. Enhanced cholesteryl-6-O-tetradecanoyl-a-D-glucopyranoside: A product of host sensitivity of LC-MS analysis of permethylated N-glycans through cholesterol efflux promoted by Helicobacter pylori. Chem Commun online purification. Electrophoresis 32:3516–3525. 48:9083–9085. Dettmann R, Ziegler T. 2011. Synthesis of octyl S-glycosides of tri- to de Leoz MLA, Young LJT, An HJ, Kronewitter SR, Kim J, Miyamoto S, pentasaccharide fragments related to the GPI anchor of Trypanosoma Borowsky AD, Chew HK, Lebrilla CB. 2011. High-mannose glycans brucei. Carbohydr Res 346:2348–2361. are elevated during breast cancer progression. Mol Cell Proteomics 10: Dewpura T, Mayne J. 2011. Analyses of PCSK9 post-translational modifica- M110.002717. tions using time-of-flight mass spectrometry. Methods Mol Biol de Leoz MLA, Gaerlan SC, Strum JS, Dimapasoc LM, Mirmiran M, 768:167–187. Tancredi DJ, Smilowitz JT, Kalanetra KM, Mills DA, German JB, Di Fabio G, Malgieri G, Isernia C, D’Onofrio J, Gaglione M, Messere A, Lebrilla CB, Underwood MA. 2012. Lacto-N-tetraose, fucosylation, Zarrelli A, De Napoli L. 2012. A novel synthetic strategy for and secretor status are highly variable in human milk oligosaccharides monosubstituted cyclodextrin derivatives. Chem Commun 48:3875– from women delivering preterm. J Proteome Res 11:4662–4672. 3877. de Medeiros Modolon S, Otsuka I, Fort S Minatti E, Borsali R, Halila S. Di Lorenzo F, Silipo A, Costello A, Sturiale L, Garozzo D, Callaghan M, 2012. Sweet block copolymer nanoparticles: Preparation and self- Lanzetta R, Parrilli M, McClean S, Molinaro A. 2012. Structural study assembly of fully oligosaccharide-based amphiphile. Biomacromole- of the lipopolysaccharide O-antigen produced by the emerging cystic cules 13:1129–1135. fibrosis pathogen Pandoraea pulmonicola. Eur J Org Chem 2243– de Oliveira AJB, GoncalvesS RAC, Chierrito TPC, dos Santos MM, de Souza 2249. LM, Gorin PAJ, Sassaki GL, Iacomini M. 2011. Structure and degree Daz-Moscoso A, Guilloteau N, Bienvenu C, Mendez-Ardoy A, Blanco JLJ, of polymerisation of fructooligosaccharides present in roots and leaves Benito JM, Le Gourrierec L, Di Giorgio C, Vierling P, Defaye J, Mellet of Stevia rebaudiana (Bert.) Bertoni. Food Chem 129:305–311. CO, Fernandez JMG. 2011. Mannosyl-coated nanocomplexes from de Paula Barbosa A, da Silva BP, Paz Parente J. 2012. A new complex amphiphilic cyclodextrins and pDNA for site-specific gene delivery. triterpenoid saponin from Samanea saman with haemolytic activity Biomaterials 32:7263–7273. and adjuvant effect. Phytochem Lett 5:626–631. Dilokpimol A, Nakai H, Gotfredsen CH, Baumann MJ, Nakai N, Hachem de Paz JL, Seeberger PH. 2012. Recent advances and future challenges in MA, Svensson B. 2011. Recombinant production and characterisation glycan microarray technology. Methods Mol Biol 808:1–12. of two related GH5 endo-b-1,4-mannanases from Aspergillus nidulans De Soyza A, Di Lorenzo F, Silipo A, Lanzetta R, Molinaro A. 2012. FGSC A4 showing distinctly different transglycosylation capacity. Lipopolysaccharide structure and biological activity from the cystic Biochim Biophys Acta 1814:1720–1729.

Mass Spectrometry Reviews DOI 10.1002/mas 129 & HARVEY

DincalpS H, Kızılok S,S Birel OH,€ I_cliS S. 2012. Synthesis and G-quadruplex Dwivedi P, Puzon G, Tam M, Langlais D, Jackson S, Kaplan K, Siems WF, binding study of a novel full visible absorbing perylene diimide dye. J Schultz AJ, Xun L, Woods AS. 2011. Metabolic profiling of Photochem Photobiol A 235:40–48. Escherichia coli by ion mobility mass spectrometry with MALDI ion Ding N, Zhang Z, Zhang W, Chun Y, Wang P, Qi H, Wang S, Li Y. 2011. source. J Mass Spectrom 45:1383–1393. Synthesis and antibacterial evaluation of a series of oligorhamnoside Dybvik AI, Norberg AL, Schute V, Soltwisch J, Jasna P-K, Va˚rum KM, derivatives. Carbohydr Res 346:2126–2135. Eijsink VGH, Dreisewerd K, Mormann M, Morten S. 2011. Analysis of Dipasquale L, d’Ippolito G, Gallo C, Vella FM, Gambacorta A, Picariello G, noncovalent chitinase-chito-oligosaccharide complexes by infrared- Fontana A. 2012. Hydrogen production by the thermophilic eubacteri- matrix assisted laser desorption ionization and nanoelectrospray ionization mass spectrometry. Anal Chem 83:4030–4036. um Thermotoga neapolitana from storage polysaccharides of the CO2- fixing diatom Thalassiosira weissflogii. Int J Hydrogen Energ Editorial. 2011. NUAP (no unnecessary acronyms please). Nat Meth 8:521. 37:12250–12257. Edlund U, Albertsson A-C. 2011. Macroinitiator halide effects in galactoglu- Dixit P, Chand K, Khan MP, Siddiqui JA, Tewari D, Ngueguim FT, comannan-mediated single electron transfer-living radical polymeriza- Chattopadhyay N, Maurya R. 2012. Phytoceramides and acylated tion. J Polym Sci A 49:4139–4145. phytosterol glucosides from Pterospermum acerifolium Willd. seed Edri-Brami M, Rosental B, Hayoun D, Welt M, Rosen H, Wirguin I, Nefussy coat and their osteogenic activity. Phytochemistry 81:117–125. B, Drory VE, Porgador A, Lichtenstein RG. 2012. Glycans in sera of Dmochowska B, Piosik J, Woziwodzka A, Sikora K, Wisniewski A, amyotrophic lateral sclerosis patients and their role in killing neuronal Wegrzyn̨ G. 2011. Mutagenicity of quaternary ammonium salts cells. PLoS One 7:e35772. containing carbohydrate moieties. J Hazard Mater 193:272–278. Egorova KS, Toukach PV. 2012. Critical analysis of CCSD data quality. J Dobruchowska JM, Gerwig GJ, Kralj S, Grijpstra P, Leemhuis H, Dijkhuizen Chem Inf Model 52:2812–2814. L, Kamerling JP. 2012. Structural characterization of linear isomalto-/ Eide KB, Norberg AL, Heggset EB, Lindbom AR, Va˚rum KM, Eijsink maltooligomer products synthesized by the novel GTFB 4,6-a- VGH, Sørlie M. 2012. Human chitotriosidase-catalyzed hydrolysis of glucanotransferase enzyme from Lactobacillus reuteri 121. Glycobiol- chitosan. Biochemistry (Moscow) 51:487–495. ogy 22:517–528. Eklof€ JM, Ruda MC, Brumer H. 2012. Distinguishing xyloglucanase activity Dodds ED. 2012. Gas-phase dissociation of glycosylated peptide ions. Mass in endo-b(1!4) glucanases. Methods Enzymol 510:97–120. Spectrom Rev 31:666–682. Elass-Rochard E, Rombouts Y, Coddeville B, Maes E, Blervaque R, Hot D, Dolashka P. 2012. Tandem mass spectrometry and glycoproteins. In: Prasain Kremer L, Guerardel Y. 2012. Structural determination and toll-like JK, editor. Tandem mass spectrometry—Applications and principles. receptor 2-dependent proinflammatory activity of dimycolyl-diara- Rijeka, Croatia: Intech. pp. 105–126. bino-glycerol from Mycobacterium marinum. J Biol Chem 287:34432– Domann P, Spencer DIR, Harvey DJ. 2012. Production and fragmentation of 34444. negative ions from neutral N-linked carbohydrates ionized by matrix- Endo T. 2011. Large-ring cyclodextrins. Trends Glycosci Glycotechnol assisted laser desorption/ionization. Rapid Commun Mass Spectrom 23:79–92. 26:469–479. Engel J, Schmalhorst PS, Routier FH. 2012. Biosynthesis of the fungal cell Dong W, Matsuno Y-k Kameyama A. 2012. A procedure for Alcian blue wall polysaccharide galactomannan requires intraluminal GDP-man- staining of mucins on polyvinylidene difluoride membranes. Anal nose. J Biol Chem 287:44418–44424. Chem 84:8461–8466. Engholm-Keller K, Larsen MR. 2011. Titanium dioxide as chemo-affinity Drake PM, Schilling B, Niles RK, Braten M, Johansen E, Liu H, Lerch M, chromatographic sorbent of biomolecular compounds—Applications Sorensen DJ, Li B, Allen S, Hall SC, Witkowska HE, Regnier FE, in acidic modification-specific proteomics. J Proteomics 75:317–328. Gibson BW, Fisher SJ. 2011. A lectin affinity workflow targeting Enkhbaatar B, Temuujin U, Lim J-H, Chi W-J, Chang Y-K, Hong S-K. 2012. glycosite-specific, cancer-related carbohydrate structures in trypsin- Identification and characterization of a xyloglucan-specific family 74 digested human plasma. Anal Biochem 408:71–85. glycosyl hydrolase from Streptomyces coelicolor A3(2). Appl Environ Dreesen IA, Fussenegger M. 2011. Ectopic expression of human mTOR Microbiol 78:607–611. increases viability, robustness, cell size, proliferation, and antibody Enomoto-Rogers Y, Kamitakahara H, Yoshinaga A, Takano T. 2012. Comb- production of Chinese hamster ovary cells. Biotechnol Bioeng shaped graft copolymers with cellulose side-chains prepared via click 108:853–866. chemistry. Carbohydr Polym 87:2237–2245. Drozdova A, BojarovaP,Krenek K, Weignerova L, Henßen B, Elling L, Enrquez-Navas PM, Chiodo F, Marradi M, Angulo J, Penades S. 2012. STD Christensen H, Jensen HH, Pelantova H, Kuzma M, Bezouska K, NMR study of the interactions between antibody 2G12 and synthetic KrupovaM,Adamek D, SlamovaK,Kren V. 2011. Enzymatic oligomannosides that mimic selected branches of gp120 glycans. synthesis of dimeric glycomimetic ligands of NK cell activation ChemBioChem 13:1357–1365. receptors. Carbohydr Res 346:1599–1609. Enugala R, Marques MMB. 2012. Synthesis of a 3-hydroxyl- free N-acetyl Dubrovskaya YV, Sova VV, Slinkina NN, Anastyuk SD, Pivkin MV, glucosamine disaccharide. Arkovic 90–100. Zvyagintseva TN. 2012. Extracellular b-D-glucosidase of the Penicilli- Esposito D, Hurevich M, Castagner B, Wang C-C, Seeberger PH. 2012. um canescens marine fungus. Appl Biochem Microbiol 48:401–408. Automated synthesis of sialylated oligosaccharides. Beilstein J Org Duchek J, Huang M-H, Vasella A. 2011. Towards stable di-carba analogues Chem 8:1601–1609. of guanofosfocins. Tetrahedron Lett 52:2940–2942. Espy C, Morelle W, Kavian N, Grange P, Goulvestre C, Viallon V, Chereau Dumarcay-Charbonnier F, Marsura A. 2012. Expeditious synthesis of bis-b- C, Pagnoux C, Michalski J-C, Guillevin L, Weill B, Batteux F, Guilpain cyclodextrinyl-diazacrown-cryptorotaxanes Chem Commun 48:732– P. 2011. Sialylation levels of anti-proteinase 3 antibodies are associated 734. with the activity of granulomatosis with polyangiitis (Wegener’s). Dupejova J, Sterba J, Vancova M, Grubhoffer L. 2011. Hemelipoglycopro- Arthritis Rheum 63:2105–2115. tein from the ornate sheep tick, Dermacentor marginatus: Structural Fahy E, Cotter D, Sud M, Subramaniam S. 2011. Lipid classification, and functional characterization. Parasites Vectors 4. Article 4 structures and tools. Biochim Biophys Acta 1811:637–647. Durantie E, Bucher C, Gilmour R. 2012. Fluorine-directed b-galactosyla- Fan S-Q, Huang W, Wang L-X. 2012. Remarkable transglycosylation activity tion: Chemical glycosylation development. Chem Eur J 18:8208–8215. of glycosynthase mutants of endo-D, an endo-b-N-acetylglucosamini- Durka M, Buffet K, Iehl J, Holler M, Nierengarten J-F, Vincent SP. 2012. dase from Streptococcus pneumoniae. J Biol Chem 287:11272–11281. The inhibition of liposaccharide heptosyltransferase WaaC with Fang T, Mo K-F, Boons G-J. 2012. Stereoselective assembly of complex multivalent glycosylated fullerenes: A new mode of glycosyltransfer- oligosaccharides using anomeric sulfonium ions as glycosyl donors. J ase inhibition. Chem Eur J 18:641–651. Am Chem Soc 134:7545–7552.

130 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Fania C, Vasso M, Torretta E, Robach P, Cairo G, Lundby C, Gelfi C. 2011. Figueiredo RT, Bittencourt VCB, Lopes LCL, Sassaki G, Barreto-Bergter Setup for human sera MALDI profiling: The case of rhEPO treatment. E. 2012. Toll-like receptors (TLR2 and TLR4) recognize polysacchar- Electrophoresis 32:1715–1727. ides of Pseudallescheria boydii cell wall. Carbohydr Res 356:260– Farid A, Pabst M, Schoberer J, Altmann F, Glossl€ J, Strasser R. 2011. 264. Arabidopsis thaliana alpha1,2-glucosyltransferase (ALG10) is re- Figueiredo TA, Sobral RG, Ludovice AM, de Almeida JMF, Bui NK, quired for efficient N-glycosylation and leaf growth. Plant J 68:314– Vollmer W, de Lencastre H, Tomasz A. 2012. Identification of genetic 325. determinants and enzymes involved with the amidation of glutamic Farizano JV, Pescaretti MdlM. Lopez FE, Hsu F-F, Delgado MA. 2012. The acid residues in the peptidoglycan of Staphylococcus aureus. PLoS PmrAB system-inducing conditions control both lipid A remodeling Pathog 8:e1002508. and O-antigen length distribution, influencing the Salmonella typhimu- Flangea C, Serb A, Sisu E, Zamfir AD. 2011. Reprint of: Chip-based rium-host interactions. J Biol Chem 287:38778–38789. nanoelectrospray mass spectrometry of brain gangliosides. Biochim Farwanah H, Kolter T. 2012. Lipidomics of glycosphingolipids. Metabolites Biophys Acta 1811:897–917. 2:134–164. Flosadottir HD, Bald I, Ingolfsson O. 2011. Fast and metastable fragmenta- Farwanah H, Kolter T, Sandhoff K. 2011. Mass spectrometric analysis of tion of deprotonated D-fructose-A combined experimental and compu- neutral sphingolipids: Methods, applications, and limitations. Biochim tational study. Int J Mass Spectrom 305:50–57. Biophys Acta 1811:854–860. Fogli A, Merle C, Roussel V, Schiffmann R, Ughetto S, Theisen M, Faunce CA, Paradies HH. 2012. Phase transformations in lipid A-diphos- Boespflug-Tanguy O. 2012. CSF N-glycan profiles to investigate phate initiated by sodium hydroxide. J Phys Chem B 116:12997– biomarkers in brain developmental disorders: Application to leukodys- 13009. trophies related to eIF2B mutations. PLoS One 7:e42688. Faunce CA, Reichelt H, Paradies HH. 2011. Studies on structures of lipid A- Fontaine T, Delangle A, Simenel C, Coddeville B, van Vliet SJ, van Kooyk monophosphate clusters. J Chem Phys 134. Article 104902 Y, Bozza S, Moretti S, Schwarz F, Trichot C, Aebi M, Delepierre M, Fauquenoy S, Hovasse A, Sloves P-J, Morelle W, Alayi TD, Slomianny C, Elbim C, Romani L, Latge J-P. 2011. Galactosaminogalactan, a new immunosuppressive polysaccharide of Aspergillus fumigatus. PLoS Werkmeister E, Schaeffer C, Van Dorsselaer A, Tomavo S. 2011. Unusual N-glycan structures required for trafficking Toxoplasma Pathog 7:e1002372. gondii GAP50 to the inner membrane complex regulate host cell entry Foong YM, Fu J, Yao SQ, Uttamchandani M. 2012. Current advances in through parasite motility. Mol Cell Proteomics 10:A111.008953. peptide and small molecule microarray technologies. Curr Opin Chem Fazekas E, Kandra L, Gyemant G. 2012. Model for b-1,6-N-acetylglucos- Biol 16:234–242. amine oligomer hydrolysis catalysed by DispersinB, a biofilm degrad- Forsberg LS, Choudhury B, Leoff C, Marston CK, Hoffmaster AR, Saile E, ing enzyme. Carbohydr Res 363:7–13. Quinn CP, Kannenberg EL, Carlson RW. 2011a. Secondary cell wall Bacillus cereus Fekete A, Borbas A, Gyemant G, Kandra L, Fazekas E, Ramasubbu N, Antus polysaccharides from strains G9241, 03BB87 and 03BB102 causing fatal pneumonia share similar glycosyl structures S. 2011. Synthesis of b-(1-6)-linked N-acetyl-D-glucosamine oligosac- Bacillus anthracis charide substrates and their hydrolysis by Dispersin B. Carbohydr Res with the polysaccharides from . Glycobiology 21:934–948. 346:1445–1453. Fekete CA, Kiss L. 2012. Purification and characterization of a recombinant Forsberg Z, Vaaje-Kolstad G, Westereng B, Bunæs AC, Stenstrøm Y, MacKenzie A, Sørlie M, Horn SJ, Eijsink VGH. 2011b. Cleavage of b-D-xylosidase from Thermobifida fusca TM51. Protein J 31:641–650. cellulose by a CBM33 protein. Protein Sci 20:1479–1483. Feliciano RP, Shea MP, Shanmuganayagam D, Krueger CG, Howell AB, Reed JD. 2012. Comparison of isolated cranberry (Vaccinium macro- Foulquier F, Amyere M, Jaeken J, Zeevaert R, Schollen E, Race V, Bammens carpon Ait.) proanthocyanidins to catechin and procyanidins A2 and R, Morelle W, Rosnoblet C, Legrand D, Demaegd D, Buist N, Cheillan B2 for use as standards in the 4-(dimethylamino)cinnamaldehyde D, Guffon N, Morsomme P, Annaert W, Freeze HH, Van Schaftingen assay. J Agric Food Chem 60:4578–4585. E, Vikkula M, Matthijs G. 2012. TMEM165 deficiency causes a congenital disorder of glycosylation. Am J Hum Genet 91:15–26. Fenn LS, McLean JA. 2011. Structural resolution of carbohydrate positional and structural isomers based on gas-phase ion mobility-mass spectrom- Franc V, Sebela M, Øehulka P, Koneitkova R, Lenobel R, Madzak C, N etry. Phys Chem Chem Phys 13:2196–2205. Kopeeny D. 2012. Analysis of -glycosylation in maize cytokinin oxidase/dehydrogenase 1 using a manual microgradient chro- Fernandez EM, Valenti V, Rockel C, Hermann C, Pot B, Boneca IG, matographic separation coupled offline to MALDI-TOF/TOF mass Grangette C. 2011. Anti-inflammatory capacity of selected lactoba- spectrometry. J Proteomics 75:4027–4037. cilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide. Gut Franceschi P, Vrhovsek U, Guella G. 2011. Ion mobility mass spectrometric 69:1050–1059. investigation of ellagitannins and their non-covalent aggregates. Rapid Commun Mass Spectrom 25:827–833. Fernandez JA, Ochoa B, Fresnedo O, Giralt MT, Rodrguez-Puertas R. 2011. Matrix-assisted laser desorption ionization imaging mass spectrometry Franceschi P, Dong Y, Strupat K, Vrhovsek U, Mattivi F. 2012. Combining in lipidomics. Anal Bioanal Chem 401:29–51. intensity correlation analysis and MALDI imaging to study the Ferranti P, Mamone G, Picariello G, Addeo F. 2011. The dark side of b- distribution of flavonols and dihydrochalcones in Golden Delicious lactoglobulin: Unedited structural features suggest unexpected func- apples. J Exp Bot 63:1123–1133. tions. J Chromatogr A 1218:3423–3431. Frank S, Geyer H, Geyer R. 2011. Microscale analysis of glycosphingolipids Ferrara C, Grau S, J€ager C, Sondermann P, Brunker€ P, Waldhauer I, Hennig from Schistosoma mansoni cercariae. J Carbohydr Chem 30:233–248. M, Ruf A, Rufer AC, Stihle M, Umana~ P, Benz J. 2011. Unique Frank S, van Die I, Geyer R. 2012. Structural characterization of carbohydrate-carbohydrate interactions are required for high affinity Schistosoma mansoni adult worm glycosphingolipids reveals pro- binding between FcgRIII and antibodies lacking core fucose. Proc Natl nounced differences with those of cercariae. Glycobiology 22:676– Acad Sci USA 108:12669–12674. 695. Ferreira JA, Domingues MRM, Reis A, Figueiredo C, Monteiro MA, Frankel MB, Schneewind O. 2012. Determinants of murein hydrolase Coimbra MA. 2011. Aldobiouronic acid domains in Helicobacter targeting to cross-wall of Staphylococcus aureus peptidoglycan. J Biol pylori. Carbohydr Res 346:638–643. Chem 287:10460–10471. Ferreira JA, Daniel-da-Silva AL, Alves RMP, Duarte D, Vieira I, Santos LL, Frankel MB, Hendrickx APA, Missiakas DM, Schneewind O. 2011. LytN, a Vitorino R, Amado F. 2011. Synthesis and optimization of lectin murein hydrolase in the cross-wall compartment of Staphylococcus functionalized nanoprobes for the selective recovery of glycoproteins aureus, is involved in proper bacterial growth and envelope assembly. J from human body fluids. Anal Chem 83:7035–7043. Biol Chem 286:32593–32605.

Mass Spectrometry Reviews DOI 10.1002/mas 131 & HARVEY

Fregolino E, Ivanova R, Lanzetta R, Molinaro A, Parrilli M, Paunova- Fukamizo T, Sato H, Mizuhara M, Ohnuma T, Gotoh T, Hiwatashi K, Krasteva T, Stoitsova SR, De Castro C. 2012. Occurrence and structure Takahashi S. 2011. Chitinase from Autographa californica multiple of cyclic Enterobacterial Common Antigen in Escherichia coli O157: nucleopolyhedrovirus: Rapid purification from Sf-9 medium and mode H-. Carbohydr Res 363:29–32. of action. Biosci Biotechnol Biochem 75:1763–1769. Freinkman E, Chng S-S, Kahne D. 2011. The complex that inserts Fukuda T, Hashimoto H, Okayasu N, Kameyama A, Onogi H, Nakagawasai lipopolysaccharide into the bacterial outer membrane forms a two- O, Nakazawa T, Kurosawa T, Hao Y, Isaji T, Tadano T, Narimatsu H, protein plug-and-barrel. Proc Natl Acad Sci USA 108:2486–2491. Taniguchi N, Gu J. 2011. a1,6-Fucosyltransferase-deficient mice Freire T, Lo-Man R, Bay S, Leclerc C. 2011. Tn glycosylation of the MUC6 exhibit multiple behavioral abnormalities associated with a schizophre- protein modulates its immunogenicity and promotes the induction of nia-like phenotype. Importance of the balance between the dopamine Th17-biased T cell responses. J Biol Chem 286:7797–7811. and serotonin systems. J Biol Chem 286:18434–18443. Frisch E, Kaup M, Egerer K, Weimann A, Tauber R, Berger M, Blanchard V. Fukuhara G, Nakamura T, Kawanami Y, Yang C, Mori T, Hiramatsu H, 2011. Profiling of endo H-released serum N-glycans using CE-LIF and Dan-oh Y, Tsujimoto K, Inoue Y. 2012. Strictly diastereocontrolled MALDI-TOF-MS - Application to rheumatoid arthritis. Electrophore- photocyclodimerization of 2-anthracenecarboxylates tethered to cyclic sis 32:3510–3515. tetrasaccharides. Chem Commun 48:9156–9158. Frohlich€ RFG, Furneaux RH, Mahuran DJ, Saf R, Stutz€ AE, Tropak MB, Fukuoka T, Yanagihara T, Imura T, Morita T, Sakai H, Abe M, Kitamoto D. Wicki J, Withers SG, Wrodnigg TM. 2011. 1-Deoxy-D-galactonojir- 2011. Enzymatic synthesis of a novel glycolipid biosurfactant, imycins with dansyl capped N-substituents as b-galactosidase inhib- mannosylerythritol lipid-D and its aqueous phase behavior. Carbohydr itors and potential probes for GM1 gangliosidosis affected cell lines. Res 346:266–271. Carbohydr Res 346:1592–1598. Fukuoka T, Yanagihara T, Imura T, Morita T, Sakai H, Abe M, Kitamoto D. Frost L, Chaudhry M, Bell T, Cohenford M. 2011. In vitro galactation of 2012. The diastereomers of mannosylerythritol lipids have different human serum albumin: Analysis of the protein’s galactation sites by interfacial properties and aqueous phase behavior, reflecting the mass spectrometry. Anal Biochem 410:248–256. erythritol configuration. Carbohydr Res 351:81–86. Fu G-M, Shi S-P, Ip FCF, Pang H-H, Ip NY. 2011a. A new carotenoid Fukuyama Y. 2011. Liquid matrices in MALDI-MS. In: Handy S, editor. glycoside from Rehmannia glutinosa. Nat Prod Res 25:1213–1218. Applications of ionic liquids in science and technology. Rijeka, Fu Y, Yin H, Wang W, Wang M, Zhang H, Zhao X, Du Y. 2011b. b-1,3- Croatia: Intech. pp. 361–374. Glucan with different degree of polymerization induced different Fung CW, Matthijs G, Sturiale L, Garozzo D, Wong KY, Wong R, Wong V, defense responses in tobacco. Carbohydr Polym 86:774–782. Jaeken J. 2012. COG5-CDG with a mild neurohepatic presentation. JIMD Rep 3:67–70. Fuchs B. 2012. Analysis of phospolipids and glycolipids by thin-layer chromatography-matrix-assisted laser desorption and ionization mass Furukawa J-I, Shinohara Y, Kuramoto H, Miura Y, Shimaoka H, Kurogochi spectrometry. J Chromatogr A 1259:62–73. M, Nakano M, Nishimura S-I. 2008. Comprehensive approach to structural and functional glycomics based on chemoselective glyco- Fuchs B, Suß€ R, Teuber K, Eibisch M, Schiller J. 2011. Lipid analysis by thin-layer chromatography - A review of the current state. J Chroma- blotting and sequential tag conversion. Anal Chem 80:1094–1101. togr A 1218:2754–2774. Furukawa J-i Fujitani N, Araki K, Takegawa Y, Kodama K, Shinohara Y. Fujii M, Sato Y, Ito H, Masago Y, Omura T. 2012. Monosaccharide 2011a. A versatile method for analysis of serine/threonine posttransla- b composition of the outer membrane lipopolysaccharide and O-chain tional modifications by -elimination in the presence of pyrazolone analogues. Anal Chem 83:9060–9067. from the freshwater cyanobacterium Microcystis aeruginosa NIES-87. J Appl Microbiol 113:896–903. Furukawa T, Hinou H, Shimawaki K, Nishimura S-I. 2011b. A potential O Fujiki R, Hashiba W, Sekine H, Yokoyama A, Chikanishi T, Ito S, Imai Y, glucuronate glycosyl donor with 2- -acyl-6,3-lactone structure: Effi- Kim J, He HH, Igarashi K, Kanno J, Ohtake F, Kitagawa H, Roeder cient synthesis of glycosaminoglycan disaccharides. Tetrahedron Lett RG, Brown M, Kato S. 2011. GlcNAcylation of histone H2B facilitates 52:5567–5570. its monoubiquitination. Nat Biotechnol 480:557–561. Furuuchi R, Yokoyama T, Watanabe Y, Hirayama M. 2011. Identification Fujita K, Sakamoto S, Ono Y, Wakao M, Suda Y, Kitahara K, Suganuma T. and quantification of short oligomeric proanthocyanidins and other 2011a. Molecular cloning and characterization of a b--arabinobiosi- polyphenols in boysenberry seeds and juice. J Agric Food Chem dase in Bifidobacterium longum that belongs to a novel glycoside 59:3738–3746. hydrolase family. J Biol Chem 286:5143–5150. Futakawa S, Nara K, Miyajima M, Kuno A, Ito H, Kaji H, Shirotani K, Honda T, Tohyama Y, Hoshi K, Hanzawa Y, Kitazume S, Imamaki R, Fujita S, Oka N, Matsumura F, Wada T. 2011b. Synthesis of oligo(a-- glycosyl phosphate) derivatives by a phosphoramidite method via Furukawa K, Tasaki K, Arai H, Yuasa T, Abe M, Arai H, Narimatsu H, N boranophosphate intermediates. J Org Chem 76:2648–2659. Hashimoto Y. 2012. A unique -glycan on human transferrin in CSF: A possible biomarker for iNPH. Neurobiol Aging 33:1807–1815. Fujita Y, Ohshima N, Hasegawa A, Schweizer F, Takeda T, Kiuchi F, Hada N. 2011c. Synthesis, inhibitory effects on nitric oxide and structure- Fyrner T, Lee H-H, Mangone A, Ekblad T, Pettitt ME, Callow ME, Callow activity relationships of a glycosphingolipid from the marine sponge JA, Conlan SL, Mutton R, Clare AS, Konradsson P, Liedberg B, Ederth Aplysinella rhax and its analogues. Molecules 16:637–651. T. 2011. Saccharide-functionalized alkanethiols for fouling-resistant self-assembled monolayers: Synthesis, monolayer properties, and Fujitani N, Takegawa Y, Ishibashi Y, Araki K, Furukawa J-I, Mitsutake S, antifouling behavior. Langmuir 27:15034–15047. Igarashi Y, Ito M, Shinohara Y. 2011. Qualitative and quantitative cellular glycomics of glycosphingolipids based on rhodococcal endo- Fyrner T, Svensson SCT, Konradsson P. 2012a. Synthesis of tri-, penta-, and glycosylceramidase-assisted glycan cleavage, glycoblotting-assisted hepta-saccharides, functionalized with orthogonally N-protected ami- sample preparation, and matrix-assisted laser desorption ionization no residues at the reducing and non-reducing ends. Tetrahedron tandem time-of-flight mass spectrometry analysis. J Biol Chem 68:6712–6720. 286:41669–41679. Fyrner T, Magnusson K, Nilsson PR, Hammarstrom€ P, Aili D, Konradsson P. Fujiwara N. 2012. Distribution, characterization of mycobacterial glycoli- 2012b. Derivatization of a bioorthogonal protected trisaccharide pids and host responses. In: Petrescu S, editor. Glycosylation. linker-toward multimodal tools for chemical biology. Bioconj Chem Shanghai: Intech. pp. 101–126. 23:1333–1340. Fujiwara S, Takahashi K. 2011. Molecular properties of mono guest-modified Gaidzik N, Kaiser A, Kowalczyk D, Westerlind U, Gerlitzki B, Sinn HP, cyclodextrins on the secondary site. Supramol Chem 23:156–159. Schmitt E, Kunz H. 2011. Synthetic antitumor vaccines containing Fujiwara N, Naka T, Ogawa M, Yamamoto R, Ogura H, Taniguchi H. 2012. MUC1 glycopeptides with two immunodominant domains-induction Characteristics of Mycobacterium smegmatis J15cs strain lipids. of a strong immune response against breast tumor tissues. Angew Tuberculosis 92:187–192. Chem Int Ed 50:9977–9981.

132 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Gaitonde V, Sucheck SJ. 2012. Synthesis of b-glycosyl amides from extrapolysaccharides of Escherichia coli. Rapid Commun Mass N-glycosyl dinitrobenzenesulfonamides. J Carbohydr Chem 31:353–370. Spectrom 26:1609–1616. Galan MC, Tran AT, Boisson J, Benito D, Butts C, Eastoe J, Brown P. 2011. Gee WJ, Hierold J, MacLellan JG, Andrews PC, Lupton DW, Junk PC. 2011. [R4N] [AOT]: A surfactant ionic liquid as a mild glycosylation Chiral lanthanoid dimers ligated by carbohydrate-based diketonates: promoter. J Carbohydr Chem 30:486–497. Catalytic and luminescent properties. Eur J Inorg Chem 3755–3760. Galan MC, Tran AT, Bromfield K, Rabbani S, Ernst B. 2012. Ionic-liquid- Geisler C, Kotu V, Sharrow M, RendicD,Poltl€ G, Tiemeyer M, Wilson IBH, based MS probes for the chemo-enzymatic synthesis of oligosacchar- Jarvis DL. 2012. The Drosophila neurally altered carbohydrate mutant ides. Org Biomol Chem 10:7091–7097. has a defective Golgi GDP-fucose transporter. J Biol Chem Galante E, Geraci C, Sciuto S, Campo VL, Carvalho I, Sesti-Costa R, Guedes 287:29599–29609. PMM, Silva JS, Hill L, Nepogodiev SA, Field RA. 2011. Glycoclusters Gellatly SL, Needham B, Madera L, Trent MS, Hancock REW. 2012. The presenting lactose on calixarene cores display trypanocidal activity. Pseudomonas aeruginosa PhoP-PhoQ two-component regulatory sys- Tetrahedron 67:5902–5912. tem is induced upon interaction with epithelial cells and controls Galvez-Lopez D, Laurens F, Quemener B, Lahaye M. 2011. Variability of cytotoxicity and inflammation. Infect Immun 80:3122–3131. cell wall polysaccharides composition and hemicellulose enzymatic Gerlach JQ, Kilcoyne M, Farrell MP, Kane M, Joshi L. 2012. Differential profile in an apple progeny. Int J Biol Macromol 49:1104–1109. release of high mannose structural isoforms by fungal and bacterial Gandolfi-Donado L, Santos M, de Lederkremer RM, Gallo-Rodriguez C. endo-b-N-acetylglucosaminidases. Mol Biosyst 8:1472–1481. 2011. Synthesis of arabinofuranose branched galactofuran tetrasac- Gerland B, Goudot A, Pourceau G, Meyer A, Dugas V, Cecioni S, Vidal S, charides, constituents of mycobacterial arabinogalactan. Org Biomol Souteyrand E, Vasseur J-J, Chevolot Y, Morvan F. 2012. Synthesis of a Chem 9:2085–2097. library of fucosylated glycoclusters and determination of their binding Gandolfi R, Marinelli F, Ragg E, Romano D, Molinari F. 2012. Chemoenzymatic toward Pseudomonas aeruginosa lectin B (PA-IIL) using a DNA-based deacylation of ramoplanin. Bioorg Med Chem Lett 22:5283–5287. carbohydrate microarray. Bioconj Chem 23:1534–1547. Gao C, Ma X, Zhang Q, Wang Q, Qu D, Tian H. 2011. A light-powered Gerland B, Goudot A, Pourceau G, Meyer A, Vidal S, Souteyrand E, Vasseur stretch-contraction supramolecular system based on cobalt coordinated J-J, Chevolot Y, Morvan F. 2012. Synthesis of homo- and heterofunc- rotaxane. Org Biomol Chem 9:1126–1132. tionalized glycoclusters and binding to Pseudomonas aeruginosa Gao J, Ma L, Liu D, Wang Z. 2012a. Microarray-based technology for lectins PA-IL and PA-IIL. J Org Chem 77:7620–7626. glycomics analysis. Comb Chem High T Scr 15:90–99. Geyer H, Schmidt M, Muller€ M, Schnabel R, Geyer R. 2012. Mass N Caenorhabditis Gao L, Gao F, Wang L, Geng C, Chi L, Zhao J, Qu Y. 2012b. N-Glycoform spectrometric comparison of -glycan profiles from elegans diversity of cellobiohydrolase I from Penicillium decumbens and mutant embryos. Glycoconj J 29:135–145. synergism of nonhydrolytic glycoform in cellulose degradation. J Biol Ghadban A, Albertin L, Rinaudo M, Heyraud A. 2012. Biohybrid Chem 287:15906–15915. glycopolymer capable of ionotropic gelation. Biomacromolecules 13:3108–3119. Garca-Alvarez I, Egido-Gabas M, Romero-Ramrez L, Doncel-Perez E, Nieto-Sampedro M, Casas J, Fernandez-Mayoralas A. 2011. Lipid and Gholipour Y, Erra-Balsells R, Nonami H. 2012. In situ pressure probe ganglioside alterations in tumor cells treated with antimitotic oleyl sampling and UVMALDI MS for profiling metabolites in living single glycoside. Mol Biosyst 7:129–138. cells. Mass Spectrom 1:A0003. Garcia-Martin F, Hinou H, Matsushita T, Hayakawa S, Nishimura S-I. 2012. Ghosh T, Misra AK. 2012. Facile synthesis of the pentasaccharide repeating An efficient protocol for the solid-phase synthesis of glycopeptides unit of the cell wall O-antigen of Escherichia coli 19ab. Carbohydr Res under microwave irradiation. Org Biomol Chem 10:1612–1617. 362:8–12. Garcia G, Naud-Martin D, Carrez D, Croisy A, Maillard P. 2011. Gil ES, Wu L, Xu L, Lowe TL. 2012. b-Cyclodextrin-poly(b-amino ester) Microwave-mediated ’click-chemistry’ synthesis of glycoporphyrin nanoparticles for sustained drug delivery across the blood-brain barrier. derivatives and in vitro photocytotoxicity for application in photody- Biomacromolecules 13:3533–3541. namic therapy. Tetrahedron 67:4924–4932. Golon A, Kuhnert N. 2012. Mass spectrometric investigation of the chemical Garenaux E, Maes E, Levêque S, Brassart C, Guerardel Y. 2011. Structural composition of caramel formed upon heating of disaccharides. J Food characterization of complex O-linked glycans from insect-derived Sci Eng 2:625–641. material. Carbohydr Res 346:1093–1104. Golon A, Kuhnert N. 2012. Unraveling the chemical composition of caramel. Garrido D, Nwosu C, Ruiz-Moyano S, Aldredge D, German JB, Lebrilla CB, J Agric Food Chem 60:3266–3274. Mills DA. 2012. Endo-b-N-acetylglucosaminidases from infant gut- Gomathinayagam S, Mitchell T, Zartler ER, Heiss C, Azadi P, Zha D, associated Bifidobacteria release complex N-glycans from human milk Houston-Cummings NR, Jiang Y, Li F, Giaccone E, Porambo RJ, glycoproteins. Mol Cell Proteomics 11:775–785. Anderson CL, Sethuraman N, Li H, Stadheim TA. 2011. Structural Gasdaska JR, Sherwood S, Regan JT, Dickey LF. 2012. An afucosylated elucidation of an a-1,2-mannosidase resistant oligosaccharide pro- anti-CD20 monoclonal antibody with greater antibody-dependent duced in Pichia pastoris. Glycobiology 21:1606–1615. cellular cytotoxicity and B-cell depletion and lower complement- Gomez-Garca M, Benito JM, Butera AP, Mellet CO, Fernandez JMG, dependent cytotoxicity than rituximab. Mol Immunol 50:134–141. Jimenez Blanco JL. 2012. Probing carbohydrate-lectin recognition in Gassler N. 2012. Methods in comprehensive mass spectrometry-based heterogeneous environments with monodisperse cyclodextrin-based measurement of sphingolipids. J Glycom Lipidom S2:002. glycoclusters. J Org Chem 77:1273–1288. Ge Z, Liu H, Zhang Y, Liu S. 2011. Supramolecular thermoresponsive Gonzalez-Perez L, Vazquez-Glara A, Perrotta L, Acosta A, Scriven SA, hyperbranched polymers constructed from poly(N-isopropylacryla- Herbert R, Cabrera JC, Francis D, Rogers HJ. 2012. Oligosaccharins mide) containing one adamantyl and two b-cyclodextrin terminal and Pectimorf(r) stimulate root elongation and shorten the cell cycle in moieties. Macromol Mol Commun 32:68–73. higher plants. Plant Growth Regul 68:211–221. Gebhart C, Ielmini MV, Reiz B, Price NL, Aas FE, Koomey M, Feldman MF. Goodfellow JJ, Baruah K, Yamamoto K, Bonomelli C, Krishna B, Harvey 2012. Characterization of exogenous bacterial oligosaccharyltransfer- DJ, Crispin M, Scanlan CN, Davis BG. 2012. An endoglycosidase with ases in Escherichia coli reveals the potential for O-linked protein alternative glycan specificity allows broadened glycoprotein remodel- glycosylation in Vibrio cholerae and Burkholderia thailandensis. ling. J Am Chem Soc 134:8030–8033. Glycobiology 22:962–974. Goodwin RJA. 2012. Sample preparation for mass spectrometry imaging: Gedda G, Gopal J, Wu H-F. 2012. Electrospray ionization and matrix- Small mistakes can lead to big consequences. J Proteomics 75:4893– assisted laser desorption/ionization mass spectrometric analysis of 4911.

Mass Spectrometry Reviews DOI 10.1002/mas 133 & HARVEY

Gopal J, Wu H-F, Gangaraju G. 2011. Quantifying the degradation of Gulcemal€ D, Alankus-S CalıS skanS O,€ Perrone A, Ozg€ ok€ ceS F, Piacente S, Bedir extracellular polysaccharides of Escherichia coli by CdS quantum E. 2011. Cycloartane glycosides from Astragalus aureus. Phytochem- dots. J Mater Chem 21:13445–13450. istry 72:761–768. Goreta SS, Dabelic S, Dumic J. 2012. Insights into complexity of congenital Gullon P, Gonzalez-Munoz~ MJ, van Gool MP, Schols HA, Hirsch J, disorders of glycosylation. Biochem Med 22:156–170. Ebringerova A, Parajo JC. 2011. Structural features and properties of Gorl€ J, Timm M, Seibel J. 2012. Mechanism-oriented redesign of an soluble products derived from Eucalyptus globulus hemicelluloses. isomaltulose synthase to an isomelezitose synthase by site-directed Food Chem 127:1798–1807. mutagenesis. ChemBioChem 13:149–156. Gunl€ M, Pauly M. 2011. AXY3 encodes a a-xylosidase that impacts the Goto-Inoue N, Hayasaka T, Zaima N, Setou M. 2011. Imaging mass structure and accessibility of the hemicellulose xyloglucan in Arabi- spectrometry for lipidomics. Biochim Biophys Acta 1811:961–969. dopsis plant cell walls. Planta 233:707–719. Gouveia R, Schaffer L, Papp S, Grammel N, Kandzia S, Head SR, Kleene R, Gunl€ M, Kraemer F, Pauly M. 2011a. Oligosaccharide mass profiling Schachner M, Conradt HS, Costa J. 2012. Expression of glycogenes in (OLIMP) of cell wall polysaccharides by MALDI-TOF/MS. Methods differentiating human NT2N neurons. Downregulation of fucosyltrans- Mol Biol 715:43–54. ferase 9 leads to decreased Lewisx levels and impaired neurite Gunl€ M, Neumetzler L, Kraemer F, de Souza A, Schultink A, Pena M, York outgrowth. Biochim Biophys Acta 1820:2007–2019. WS, Paulya M. 2011b. AXY8 Encodes an a-fucosidase, underscoring Grabosch C, Hartmann M, Schmidt-Lassen J, Lindhorst TK. 2011. Squaric the importance of apoplastic metabolism on the fine structure of acid monoamide mannosides as ligands for the bacterial lectin FimH: Arabidopsis cell wall polysaccharides. Plant Cell 23:4025–4040. Covalent inhibition or not?. ChemBioChem 12:1066–1074. Guo J, Ogier JR, Desgranges S, Darcy R, O’Driscoll C. 2012a. Anisamide- Grabosch C, Kolbe K, Lindhorst TK. 2012. Glycoarrays by a new tandem targeted cyclodextrin nanoparticles for siRNA delivery to prostate noncovalent-covalent modification of polystyrene microtiter plates and tumours in mice. Biomaterials 33:7775–7784. their interrogation with live cells. ChemBioChem 13:1874–1879. Guo Q, Cui SW, Wang Q, Hu X, Kang J, Yada RY. 2012b. Structural Graham SA, Antonopoulos A, Hitchen PG, Haslam SM, Dell A, Drickamer characterization of a low-molecular-weight heteropolysaccharide (glu- K, Taylor ME. 2011. Identification of neutrophil granule glycoproteins comannan) isolated from Artemisia sphaerocephala Krasch. Carbo- as Lewisx-containing ligands cleared by the scavenger receptor C-type hydr Res 350:31–39. lectin. J Biol Chem 286:24336–24349. Gupta V, Bhinge KN, Hosain SB, Xiong K, Gu X, Shi R, Ho M-Y, Khoo K- Grass J, Pabst M, Kolarich D, Poltl G, Leonard R, Brecker L, Altmann F. H, Li S-C, Li Y-T, Ambudkar SV, Jazwinski SM, Liu Y-Y. 2012. 2011. Discovery and structural characterization of fucosylated oligo- Ceramide glycosylation by glucosylceramide synthase selectively mannosidic N-glycans in mushrooms. J Biol Chem 286:5977–5984. maintains the properties of breast cancer stem cells. J Biol Chem Greenfield LK, Richards MR, Li J, Wakarchuk WW, Lowary TL, Whitfield 287:37195–37205. C. 2012. Biosynthesis of the polymannose lipopolysaccharide O- Gur’eva LY, Bol’sheborodova AK, Sebyakin YL. 2012. Design, synthesis, antigens from Escherichia coli serotypes O8 and O9a requires a unique and properties of neoglycolipids based on ethylene glycoles conjugated combination of single- and multiple-active site mannosyltransferases. J with lactose as components of targeted delivery systems of biologically Biol Chem 287:35078–35091. active compounds. Russ J Org Chem 48:1047–1054. Grigorian A, Araujo L, Naidu NN, Place DJ, Choudhury B, Demetriou M. Ha M, In Y, Maeng H, Zee OP, Lee J, Kim Y. 2011a. Development of a 2011. N-Acetylglucosamine inhibits T-helper 1 (Th1)/T-helper 17 matrix-prespotted plate for enhancing the reproducibility of serum (Th17) cell responses and treats experimental autoimmune encephalo- glycan analysis by MALDI-TOF-MS. Mass Spectrom Lett 2:61–64. myelitis. J Biol Chem 286:40133–40141. Ha S, Wang Y, Rustandi RR. 2011b. Biochemical and biophysical characteriza- Guan W, Ban L, Cai L, Li L, Chen W, Liu X, Mrksich M, Wang PG. 2011. tion of humanized IgG1 produced in Pichia pastoris. mAbs 3:453–460. Combining carbochips and mass spectrometry to study the donor Ha M, Kwak JH, Kim Y, Zee OP. 2012. Direct analysis for the distribution specificity for the Neisseria meningitidis b1,3-N-acetylglucosaminyl- of toxic glycoalkaloids in potato tuber tissue using matrix-assisted transferase LgtA. Bioorg Med Chem Lett 21:5025–5028. laser desorption/ionization mass spectrometric imaging. Food Chem Guchhait G, Misra AK. 2011. Convergent synthesis of a common 133:1155–1162. pentasaccharide corresponding to the O-antigen of Escherichia coli Haag AF, Wehmeier S, Muszynski A, Kerscher B, Fletcher V, Berry SH, O168 and Shigella dysenteriae type 4. Glycoconj J 28:11–19. Hold GL, Carlson RW, Ferguson GP. 2011. Biochemical characteriza- Guedes S, Vitorino R, Domingues MRM, Amado F, Domingues P. 2011. tion of Sinorhizobium meliloti mutants reveals gene products involved Glycation and oxidation of histones H2B and H1: In vitro study and in the biosynthesis of the unusual lipid A very long-chain fatty acid. J characterization by mass spectrometry. Anal Bioanal Chem 399:3529– Biol Chem 286:17455–17466. 3539. Hagiwara M, Dohi M, Nakahara Y, Komatsu K, Asahina Y, Ueki A, Hojo H, Guerardel Y, Chang L-Y, Fujita A, Coddeville B, Maes E, Sato C, Harduin- Nakahara Y, Ito Y. 2011. Synthesis of biantennary complex-type Lepers A, Kubokawa K, Kitajima K. 2012. Sialome analysis of the nonasaccharyl Asn building blocks for solid-phase glycopeptide cephalochordate Branchiostoma belcheri, a key organism for verte- synthesis. J Org Chem 76:5229–5239. brate evolution. Glycobiology 22:479–491. Hahne H, Neubert P, Kuhn K, Etienne C, Bomgarden R, Rogers JC, Kuster€ Guillard M, Morava E, van Delft FL, Hague R, Korner€ C, Adamowicz M, B. 2012. Carbonyl-reactive tandem mass tags for the proteome-wide Wevers RA, Lefeber DJ. 2011a. Plasma N-glycan profiling by mass quantification of N-linked glycans. Anal Chem 84:3716–3724. spectrometry for congenital disorders of glycosylation type II. Clin Hajjar AM, Ernst RK, Fortuno ES, Brasfield AS, Yam CS, Newlon LA, Chem 57:593–602. Kollmann TR, Miller SI, Wilson CB. 2012. Humanized TLR4/MD-2 Guillard M, Morava E, de Ruijter J, Roscioli T, Penzien J, van den Heuvel L, mice reveal LPS recognition differentially impacts susceptibility to Willemsen MA, de Brouwer A, Bodamer OA, Wevers RA, Lefeber DJ. Yersinia pestis and Salmonella enterica. PLoS Pathog 8:e1002963. 2011b. B4GALT1-Congenital disorders of glycosylation presents as a Halfinger B, Sarg B, Lindner HH. 2011. Evaluation of non-reductive b- non-neurologic glycosylation disorder with hepatointestinal involve- elimination/Michael addition for glycosylation site determination in ment. J Pediatr 159:1041–1043. mucin-like O-glycopeptides. Electrophoresis 32:3546–3553. Guillard M, Wada Y, Hansikova H, Yuasa I, Vesela K, Ondruskova N, Hall M, Rubin J, Behrens SH, Bommarius AS. 2011. The cellulose-binding Kadoya M, Janssen A, Van den Heuvel LPWJ, Morava E, Zeman J, domain of cellobiohydrolase Cel7A from Trichoderma reesei is also a Wevers RA, Lefeber DJ. 2011c. Transferrin mutations at the glycosyla- thermostabilizing domain. J Biotechnol 155:370–376. tion site complicate diagnosis of congenital disorders of glycosylation Hamad MA, Di Lorenzo F, Molinaro A, Valvano MA. 2012. Aminoarabinose type I. J Inherit Metab Dis 34:901–906. is essential for lipopolysaccharide export and intrinsic antimicrobial

134 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

peptide resistance in Burkholderia cenocepacia. Mol Microbiol Harvey DJ. 2009. Analysis of carbohydrates and glycoconjugates by matrix- 85:962–974. assisted laser desorption/ionization mass spectrometry: An update for Hamed AI, Masullo M, Sheded MG, Mahalel UA, Tawfik MM, Perrone A, 2003-2004. Mass Spectrom Rev 28:273–361. Piacente S. 2011. Triterpene saponins from Salsola imbricata. Harvey DJ. 2011. Analysis of carbohydrates and glycoconjugates by matrix- Phytochem Lett 4:353–356. assisted laser desorption/ionization mass spectrometry: An update for Hamed A, Perrone A, Mahalel U, Oleszek W, Stochmal A, Piacente S. 2012. the period 2005-2006. Mass Spectrom Rev 30:1–100. Oleanane glycosides from the roots of Alhagi maurorum. Phytochem Harvey DJ. 2011b. Derivatization of carbohydrates for analysis by chroma- Lett 5:782–787. tography, electrophoresis and mass spectrometry. J Chromatogr B Han J, Jiang X, Zhang L. 2011. Optimisation of extraction conditions for 879:1196–1225. polysaccharides from the roots of Isatis tinctoria L. by response surface Harvey DJ. 2012. Analysis of carbohydrates and glycoconjugates by matrix- methodology and their in vitro free radicals scavenging activities and assisted laser desorption/ionization mass spectrometry: An update for effects on IL-4 and IFN-g mRNA expression in chicken lymphocytes. 2007-2008. Mass Spectrom Rev 31:183–311. Carbohydr Polym 86:1320–1326. Harvey DJ. 2015. In Press Analysis of carbohydrates and glycoconjugates by Han H, Stapels M, Ying W, Yu Y, Tang L, Jia W, Chen W, Zhang Y, Qian X. matrix-assisted laser desorption/ionization mass spectrometry: An 2012a. Comprehensive characterization of the N-glycosylation status update for 2009-2010. Mass Spectrom Rev 34:268–422. of CD44s by use of multiple mass spectrometry-based techniques. Harvey DJ, Rudd PM. 2011. Fragmentation of negative ions from N-linked Anal Bioanal Chem 404:373–388. carbohydrates. Part 5: Anionic N-linked glycans. Int J Mass Spectrom Han S, Kanamoto T, Nakashima H, Yoshida T. 2012b. Synthesis of a new 305:120–130. amphiphilic glycodendrimer with antiviral functionality. Carbohydr Harvey DJ, Royle L, Radcliffe CM, Rudd PM, Dwek RA. 2008. Structural Polym 90:1061–1068. and quantitative analysis of N-linked glycans by MALDI and negative Han W, Zhao S, Liu H, Wu Z, Gu Q, Li Y. 2012c. Isolation, identification and ion nanospray mass spectrometry. Anal Biochem 376:44–60. agarose degradation of a polysaccharide-degrading marine bacterium Harvey DJ, Merry AH, Royle L, Campbell MP, Dwek RA, Rudd PM. 2009. Persicobacter sp. JZB09. Acta Microbiol Sinica 52:776–783. Proposal for a standard system for drawing structural diagrams of N- Han W, Gu J, Yan Q, Li J, Wu Z, Gu Q, Li Y. 2012d. A polysaccharide- and O-linked carbohydrates and related compounds. Proteomics degrading marine bacterium Flammeovirga sp. MY04 and its extracel- 9:3796–3801. lular agarase system. J Ocean Univ China 11:375–382. Harvey DJ, Merry AH, Royle L, Campbell MP, Rudd PM. 2011a. Symbol Han X, Yang K, Gross RW. 2012e. Multi-dimensional mass spectrometry- nomenclature for representing glycan structures: Extension to cover based shotgun lipidomics and novel strategies for lipidomic analyses. different carbohydrate types. Proteomics 11:4291–4295. Mass Spectrom Rev 31:134–178. Harvey DJ, Sobott F, Crispin M, Wrobel A, Bonomelli C, Vasiljevic S, Hanisch F-G. 2011. Top-down sequencing of O-glycoproteins by in-source Scanlan CN, Scarff C, Thalassinos K, Scrivens JH. 2011b. Ion mobility decay matrix-assisted laser desorption ionization mass spectrometry mass spectrometry for extracting spectra of N-glycans directly from for glycosylation site analysis. Anal Chem 83:4829–4837. incubation mixtures following glycan release: Application to glycans Hanisch F-G. 2012. O-Glycoproteomics: Site-specific O-glycoprotein analy- from engineered glycoforms of intact, folded HIV gp120. J Am Soc sis by CID/ETD electrospray ionization tandem mass spectrometry and Mass Spectrom 22:568–581. top-down glycoprotein sequencing by in-source decay MALDI mass Harvey DJ, Scarff CA, Crispin M, Scanlan CN, Bonomelli C, Scrivens JH. spectrometry. Methods Mol Biol 842:179–189. 2012. MALDI-MS/MS with traveling wave ion mobility for the Hankins JV, Madsen JA, Giles DK, Childers BM, Klose KE, Brodbelt JS, structural analysis of N-linked glycans. J Am Soc Mass Spectrom Trent MS. 2011. Elucidation of a novel Vibrio cholerae lipid A 23:1955–1966. secondary hydroxy-acyltransferase and its role in innate immune Hasan N, Gopal J, Wu H-F. 2011. Rapid, sensitive and direct analysis of recognition. Mol Microbiol 81:1313–1329. exopolysaccharides from biofilm on aluminum surfaces exposed to sea Hankins JV, Madsen JA, Giles DK, Brodbelt JS, Trent MS. 2012. Amino water using MALDI-TOF MS. J Mass Spectrom 46:1160–1167. acid addition to Vibrio cholerae LPS establishes a link between surface Hasehira K, Tateno H, Onuma Y, Ito Y, Asashima M, Hirabayashi J. 2012. remodeling in Gram-positive and Gram-negative bacteria. Proc Natl Structural and quantitative evidence for dynamic glycome shift on Acad Sci USA 109:8722–8727. production of induced pluripotent stem cells. Mol Cell Proteomics Hansen SU, Miller GJ, Barath M, Broberg KR, Avizienyte E, Helliwell M, 11:1913–1923. Raftery J, Jayson GC, Gardiner JM. 2012. Synthesis and scalable Hashiguchi T, Mizumoto S, Nishimura Y, Tamura J-I, Yamada S, Sugahara conversion of L-iduronamides to heparin-related di- and tetrasacchar- K. 2011. Involvement of human natural killer-1 (HNK-1) sulfotransfer- ides. J Org Chem 77:7823–7843. ase in the biosynthesis of the GlcUA(3-O-sulfate)-Gal-Gal-Xyl tetra- Harrison R, Hitchen PG, Panico M, Morris HR, Mekhaiel D, Pleass RJ, Dell saccharide found in a-thrombomodulin from human urine. J Biol A, Hewitt JE, Haslam SM. 2012. Glycoproteomic characterization of Chem 286:33003–33011. recombinant mouse a-dystroglycan. Glycobiology 22:662–675. Hashimoto A, Shimono K, Horikawa Y, Ichikawa T, Wada M, Imai T, Hart C, Chase LG, Hajivandi M, Agnew B. 2011. Metabolic labeling and Sugiyama J. 2011a. Extraction of cellulose-synthesizing activity of click chemistry detection of glycoprotein markers of mesenchymal Gluconacetobacter xylinus by alkylmaltoside. Carbohydr Res stem cell differentiation. Methods Mol Biol 698:459–484. 346:2760–2768. Hartley MD, Morrison MJ, Aas FE, Børud B, Koomey M, Imperiali B. 2011. Hashimoto R, Fujitani N, Takegawa Y, Kurogochi M, Matsushita T, Naruchi Biochemical characterization of the O-linked glycosylation pathway K, Ohyabu N, Hinou H, Gao XD, Manri N, Satake H, Kaneko A, in Neisseria gonorrhoeae responsible for biosynthesis of protein glycans Sakamoto T, Nishimura S-I. 2011b. An efficient approach for the containing NN’-diacetylbacillosamine. Biochemistry 50: 4936–4948. characterization of mucin-type glycopeptides: The effect of O- Harvey DJ. 1999. Matrix-assisted laser desorption/ionization mass spec- glycosylation on the conformation of synthetic mucin peptides. Chem trometry of carbohydrates. Mass Spectrom Rev 18:349–451. Eur J 17:2393–2404. Harvey DJ. 2006. Analysis of carbohydrates and glycoconjugates by matrix- Hashimoto M, Tanishita Y, Suda Y, Murakami E-i Nagata M, Kucho K-i Abe assisted laser desorption/ionization mass spectrometry: An update M, Uchiumi T. 2012. Characterization of nitric oxide-inducing lipid A covering the period 1999-2000. Mass Spectrom Rev 25:595–662. derived from Mesorhizobium loti lipopolysaccharide. Microbes Envi- Harvey DJ. 2008. Analysis of carbohydrates and glycoconjugates by matrix- ron 27:490–496. assisted laser desorption/ionization mass spectrometry: An update Hassan HMA, Maltman BA. 2012. Mixed SAMs and MALDI-ToF MS: covering the period 2001-2002. Mass Spectrom Rev 27:125–201. Preparation of N-glycosylamine derivative and thioctic acid methyl

Mass Spectrometry Reviews DOI 10.1002/mas 135 & HARVEY

ester bearing 1,2-dithiolane groups and detection of enzymatic reaction Hirai H, Takai R, Iwano M, Nakai M, Kondo M, Takayama S, Isogai A, Che F-S. on Au. Bioorg Chem 40:6–9. 2011. Glycosylation regulates specific induction of rice immune responses Hatanaka K. 2012. Incorporation of fluorous glycosides to cell membrane by Acidovorax avenae flagellin. J Biol Chem 286:25519–25530. and saccharide chain elongation by cellular enzymes. Topics Curr Hirano K, Arayaveerasid S, Seki K, Adams DJ, Mitsutomi M. 2012. Chem 308:291–306. Characterization of a chitosanase from Aspergillus fumigatus Hattori T, Ogata M, Kameshima Y, Totani K, Nikaido M, Nakamura T, ATCC13073. Biosci Biotechnol Biochem 76:1523–1528. Koshino H, Usui T. 2012a. Enzymatic synthesis of cellulose II-like Hirasawa Y, Sakai T, Ito M, Yoshimura H, Feng Y, Nagamatsu T. 2011. substance via cellulolytic enzyme-mediated transglycosylation in an Advanced-glycation-end-product-cholesterol-aggregated-protein ac- aqueous medium. Carbohydr Res 353:22–26. celerates the proliferation of mesangial cells mediated by transform- Hattori T, Sakabe Y, Ogata M, Michishita K, Dohra H, Kawagishi H, Totani ing-growth-factor-beta 1 receptors and the ERK-MAPK pathway. Eur J K, Nikaido M, Nakamura T, Koshino H, Usui T. 2012b. Enzymatic Pharmacol 672:159–168. synthesis of an a-chitin-like substance via lysozyme-mediated trans- Hirayama H, Suzuki T. 2011. Metabolism of free oligosaccharides is glycosylation. Carbohydr Res 347:16–22. facilitated in the och1D mutant of Saccharomyces cerevisiae. Glycobi- Hayee BH, Antonopoulos A, Murphy EJ, Rahman FZ, Sewell G, Smith BN, ology 21:1341–1348. McCartney S, Furman M, Hall G, Bloom SL, Haslam SM, Morris HR, Hirose K, Amano M, Hashimoto R, Lee YC, Nishimura S-I. 2011. Insight Boztug K, Klein C, Winchester B, Pick E, Linch DC, Gale RE, Smith into glycan diversity and evolutionary lineage based on comparative AM, Dell A, Segal AW. 2011. G6PC3 Mutations are associated with a avio-N-glycomics and sialic acid analysis of 88 egg whites of major defect of glycosylation: a novel mechanism for neutrophil galloanserae. Biochemistry 50:4757–4774. dysfunction. Glycobiology 21:914–924. Hjørringgaard CU, Vad BS, Matchkov VV, Nielsen SB, Vosegaard T, Nielsen Hayoun D, Kapp T, Edri-Brami M, Ventura T, Cohen M, Avidan A, NC, Otzen DE, Skrydstrup T. 2012. Cyclodextrin-scaffolded alamethi- Lichtenstein RG. 2012. HSP60 is transported through the secretory cin with remarkably efficient membrane permeabilizing properties and pathway of 3-MCA-induced fibrosarcoma tumour cells and undergoes membrane current conductance. J Phys Chem B 116:7652–7659. N-glycosylation. FEBS J 279:2083–2095. Ho Y-P, Reddy PM. 2011. Advances in mass spectrometry for the He N, Wang R, He Y, Dang X. 2012a. Fabrication, structure and surface identification of pathogens. Mass Spectrom Rev 30:1203–1224. charges of albumin-chitosan hybrids. Sci China Chem 55:1788–1795. Ho SCL, Bardor M, Feng H, Mariati, Tong YW, Song Z, Yap MGS, Yang Y. He X, Haselhorst T, von Itzstein M, Kolarich D, Packer NH, Kermode AR. 2012. IRES-mediated tricistronic vectors for enhancing generation of 2012b. Influence of an ER-retention signal on the N-glycosylation of high monoclonal antibody expressing CHO cell lines. J Biotechnol recombinant human a-L-iduronidase generated in seeds of Arabidopsis. 157:130–139. Plant Mol Biol 79:157–169. Hocquelet C, Jankowski CK, Pelletier AL, Tabet J-C, Lamouroux C, Heiss C, Wang Z, Azadi P. 2011. Sodium hydroxide permethylation of Berthault P. 2011. Synthesis and inclusion properties study of some heparin disaccharides. Rapid Commun Mass Spectrom 25:774–778. mono 6-amino-b-cyclodextrin dimers bridged by NN-succinyldiamide Heiss C, Burtnick MN, Wang Z, Azadi P, Brett PJ. 2012. Structural analysis linkers. J Incl Phenom Macrocyl Chem 69:75–84. of capsular polysaccharides expressed by Burkholderia mallei and Hoffmann-Roder€ A, Johannesy M. 2011. Synthesis of a MUC1-glycopep- Burkholderia pseudomallei. Carbohydr Res 349:90–94. tide-BSA conjugate vaccine bearing the 3’-deoxy-3’-fluoro-Thomsen- Henderson G, Ulsemer P, Schober€ U, Loffler€ A, Alpert C-A, Zimmermann- Friedenreich antigen. Chem Commun 47:9903–9905. Kordmann M, Reutter W, Karsten U, Goletz S, Blaut M. 2011a. Hoffmann-Roder€ A, Schoenhentz J, Wagner S, Schmitt E. 2011. Perfluor- Occurrence of the human tumor-specific antigen structure Galb1- oalkylated amphiphilic MUC1 glycopeptide antigens as tools for 3GalNAca- (Thomsen-Friedenreich) and related structures on gut cancer immunotherapy. Chem Commun 47:382–384. bacteria: Prevalence, immunochemical analysis and structural confir- Hoffmann BR, Liu Y, Mosher DF. 2012. Modification of EGF-like module 1 mation. Glycobiology 21:1277–1289. of thrombospondin-1, an animal extracellular protein, by O-linked N- Henderson GE, Isett KD, Gerngross TU. 2011b. Site-specific modification of acetylglucosamine. PLoS One 7:e32762. recombinant proteins: A novel platform for modifying glycoproteins Hojo H, Tanaka H, Hagiwara M, Asahina Y, Ueki A, Katayama H, Nakahara expressed in E. coli. Bioconj Chem 22:903–912. Y, Yoneshige A, Matsuda J, Ito Y, Nakahara Y. 2012. Chemoenzymatic Henquet M, Eigenhuijsen J, Hesselink T, Spiegel H, Schreuder M, van Duijn synthesis of hydrophobic glycoprotein: Synthesis of saposin C carrying E, Cordewener J, Depicker A, van der Krol A, Bosch D. 2011. complex-type carbohydrate. J Org Chem 77:9437–9446. Characterization of the single-chain Fv-Fc antibody MBP10 produced Holck J, Lorentzen A, Vigsnæs LK, Licht TR, Mikkelsen JD, Meyer AS. in Arabidopsis alg3 mutant seeds. Transgenic Res 20:1033–1042. 2011a. Feruloylated and nonferuloylated arabino-oligosaccharides Herbert AP, Kavanagh D, Johansson C, Morgan HP, Blaum BS, Hannan JP, from sugar beet pectin selectively stimulate the growth of Bifidobacte- Barlow PN, Uhrn D. 2012. Structural and functional characterization rium spp. in human fecal in vitro fermentations. J Agric Food Chem of the product of disease-related factor H gene conversion. Biochemis- 59:6511–6519. try (Moscow) 51:1874–1884. Holck J, Hjernø K, Lorentzen A, Vigsnæs LK, Hemmingsen L, Licht TR, Herczeg M, Lazar L, Mandi A, Borbas A, Komaromi I, Liptak A, Antus S. Mikkelsen JD, Meyer AS. 2011b. Tailored enzymatic production of 2011. Synthesis of disaccharide fragments of the AT-III binding oligosaccharides from sugar beet pectin and evidence of differential domain of heparin and their sulfonatomethyl analogues. Carbohydr effects of a single DP chain length difference on human faecal Res 346:1827–1836. microbiota composition after in vitro fermentation. Proc Biochem Herczeg M, Lazar L, Bereczky Z, KcvS or€ KE, Timari I, Kappelmayer J, 46:1039–1049. Liptak A, Antus S, Aniko B. 2012. Synthesis and anticoagulant activity Holm R, Madsen JC, Shi W, Larsen KL, St€ade LW, Westh P. 2011. of bioisosteric sulfonic-acid analogues of the antithrombin-binding Thermodynamics of complexation of tauro- and glyco-conjugated bile pentasaccharide domain of heparin. Chem Eur J 18:10643–10652. salts with two modified b-cyclodextrins. J Incl Phenom Macrocyl Hidaka H, Takiwaki M, Yamashita M, Otsuki S, Kawasaki K, Sugano M, Chem 69:201–211. Honda T. 2012. Mild acid hydrolysis of sphingolipids yields lysosphin- Holten-Andersen L, Thaysen-Andersen M, Jensen SB, Buchwald C, Højrup golipids: A matrix-assisted laser desorption and ionization time-of- P, Offenberg H, Nielsen HJ, Brunner€ N, Nauntofte B, Reibel J. 2011. flight mass spectrometry study. J Anal Biosci 35:241–248. Salivary tissue inhibitor of metalloproteinases-1 localization and Hijazi M, Durand J, Pichereaux C, Pont F, Jamet E, Albenne C. 2012. glycosylation profile analysis. Acta Path Micro Im 119:741–749. Characterization of the arabinogalactan protein 31 (AGP31) of Hopf PS, Ford RS, Zebian N, Merkx-Jacques A, Vijayakumar S, Ratnayake Arabidopsis thaliana. New advances on the Hyp-O-glycosylation of D, Hayworth J, Creuzenet C. 2011. Protein glycosylation in Helico- the Pro-rich domain. J Biol Chem 287:9623–9632. bacter pylori: Beyond the flagellins? PLoS One 6:e25722.

136 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Horikoshi S, Minami D, Ito S, Sakai H, Kitamoto D, Abe M, Serpone N. Huang Z-H, Shi L, Ma J-W, Sun Z-Y, Cai H, Chen Y-X, Zhao Y-F, Li Y-M. 2011. Molecular dynamics simulations of adsorption of hydrophobic 2012d. A totally synthetic, self-assembling, adjuvant-free MUC1 1,2,4-trichlorobenzene (TCB) on hydrophilic TiO2 in surfactant glycopeptide vaccine for cancer therapy. J Am Chem Soc 134:8730– emulsions and experimental process efficiencies of photo-degradation 8733. and -dechlorination. J Photochem Photobiol A 217:141–146. Hudak JE, Yu HH, Bertozzi CR. 2011. Protein glycoengineering enabled by Horn PJ, Chapman KD. 2012. Lipidomics in tissues, cells and subcellular the versatile synthesis of aminooxy glycans and the genetically compartments. Plant J 70:69–80. encoded aldehyde tag. J Am Chem Soc 133:16127–16135. Horo I, Bedir E, Masullo M, Piacente S, Ozg€ ok€ ceS F, Alankus-S CalıS skanS O.€ Hug I, Zheng B, Reiz B, Whittal RM, Fentabil MA, Klassen JS, Feldman 2012. Saponins from Astragalus hareftae (NAB.) SIRJ. Phytochem MF. 2011. Exploiting bacterial glycosylation machineries for the Lett 84:147–153. synthesis of a Lewis antigen-containing glycoprotein. J Biol Chem Horowitz ED, Weinberg MS, Asokan A. 2011. Glycated AAV vectors: 286:37887–37894. Chemical redirection of viral tissue tropism. Bioconj Chem 22:529– Hughey CA, Hendrickson CL, Rodgers RP, Marshall AG, Qian K. 2001. 532. Kendrick mass defect spectrum: a compact visual analysis for Howard LR, Prior RL, Liyanage R, Lay JO. 2012. Processing and storage ultrahigh-resolution broadband mass spectra. Anal Chem 73:4676– effect on berry polyphenols: Challenges and implications for bioactive 4681. properties. J Agric Food Chem 60:6678–6693. Hulsmeier€ AJ, Welti M, Hennet T. 2011. Glycoprotein maturation and the Hreggvidsson GO, Dobruchowska JM, Fridjonsson OH, Jonsson JO, Gerwig UPR. Methods Enzymol 491:163–182. GJ, Aevarsson A, Kristjansson JK, Curti D, Redgwell RR, Hansen C-E, Hung S-C, Lu X-A, Lee J-C, Chang MD-T, Fang S-I, Fan T-C, Zulueta Kamerling JP, Debeche-Boukhit T. 2011. Exploring novel non-Leloir b- MML, Zhong Y-Q. 2012a. Synthesis of heparin oligosaccharides and glucosyltransferases from proteobacteria for modifying linear (b1!3)- their interaction with eosinophil-derived neurotoxin. Org Biomol linked gluco-oligosaccharide chains. Glycobiology 21:304–328. Chem 10:760–772. Hsieh YSY, Harris PJ. 2012. Structures of xyloglucans in primary cell walls Hung W-T, Wang S-H, Chen Y-T, Yu H-M, Chen C-H, Yang W-B. 2012b. of gymnosperms, monilophytes (ferns sensu lato) and lycophytes. MALDI-TOF MS analysis of native and permethylated or benzimid- Phytochemistry 79:87–101. azole-derivatized polysaccharides. Molecules 17:4950–4961. Hsu Y, Lu X-A, Zulueta MML, Tsai C-M, Lin K-I, Hung S-C, Wong C-H. Huybrechts S, De Laet C, Bontems P, Rooze S, Souayah H, Sznajer Y, 2012. Acyl and silyl group effects in reactivity-based one-pot Sturiale L, Garozzo D, Matthijs G, Ferster A, Jaeken J, Goyens P. 2012. glycosylation: Synthesis of embryonic stem cell surface carbohydrates Deficiency of subunit 6 of the conserved oligomeric Golgi complex Lc4 and IV2Fuc-Lc4. J Am Chem Soc 134:4549–4552. (COG6-CDG): Second patient, different phenotype. JIMD Rep 4:103– Hu Y, Mechref Y. 2012. Comparing MALDI-MS, RP-LC-MALDI-MS and 108. RP-LC-ESI-MS glycomic profiles of permethylated N-glycans derived Hwang IH, Kim DW, Kim SJ, Min BS, Lee SH, Son JK, Kim C-H, Chang from model glycoproteins and human blood serum. Electrophoresis HW, Na M. 2011. Asterosaponins isolated from the starfish Asterias 33:1768–1777. amurensis. Chem Pharm Bull 59:78–83. Hu J-B, Zhang P, Wang M-X, Zhou F, Niu Y-S, Miao Y-G. 2012. A Ichimura N, Kasama T. 2012. Identification of valine- or leucine-containing transgenic Bm cell line of piggyBac transposon-derived targeting glycopeptidolipids from Mycobacterium avium-intracellulare com- expression of humanized glycoproteins through N-glycosylation. Mol plex. Curr Microbiol 64:561–568. Biol Rep 39:8405–8413. Ichiyanagi T, Fukunaga M, Tagashira R, Hayashi S, Nanjo M, Yamasaki R. Hua S, An HJ. 2012. Glycoscience aids in biomarker discovery. BMB Rep 2011. A new Kdo derivative for the synthesis of an inner-core 45:323–330. disaccharide of lipopolysaccharides and lipooligosaccharides. Tetrahe- dron 67:5964–5971. Huang H, Guo H, Xue M, Liu Y, Yang J, Liang X, Chu C. 2011a. Click novel glycosyl amino acid hydrophilic interaction chromatography stationary Ielmini MV, Feldman MF. 2011. Desulfovibrio desulfuricans PglB homolog phase and its application in enrichment of glycopeptides. Talanta possesses oligosaccharyltransferase activity with relaxed glycan speci- 85:1642–1647. ficity and distinct protein acceptor sequence requirements. Glycobiol- Huang K-T, Gorska K, Alvarez S, Barluenga S, Winssinger N. 2011b. ogy 21:734–742. Combinatorial self-assembly of glycan fragments into microarrays. Iglesias-Gonzalez T, Sanchez-Gonzalez C, Montes-Bayon M, Llopis- ChemBioChem 12:56–60. Gonzalez J, Sanz-Medel A. 2012. Absorption, transport and insulin- bis Huang W, Li J, Wang L-X. 2011c. Unusual transglycosylation activity of mimetic properties of (maltolato) oxovanadium (IV) in streptozotocin-induced hyperglycemic rats by integrated mass spectrometric Flavobacterium meningosepticum endoglycosidases enables convergent chemoenzymatic synthesis of core fucosylated complex N- techniques. Anal Bioanal Chem 402:277–285. glycopeptides. ChemBioChem 12:932–941. Iino K, Iwamoto S, Kasahara Y, Matsuda K, Tonozuka T, Nishikawa A, Ito Y, Matsuo I. 2012. Facile construction of 1,2-cis glucosidic linkage using Huang Y-L, Tsujita T, Tanaka T, Matsuo Y, Kouno I, Li D-P, Nonaka G-I. sequential oxidation-reduction route for synthesis of an ER processing 2011d. Triterpene hexahydroxydiphenoyl esters and a quinic acid a-glucosidase I substrate. Tetrahedron Lett 53:4452–4456. purpurogallin carbonyl ester from the leaves of Castanopsis fissa. Phytochem Lett 72:2006–2014. Ikeda A, Aono R, Maekubo N, Katao S, Kikuchi J-i Akiyama M. 2011. Pseudorotaxane structure of a fullerene derivative-cyclodextrin 1:2 Huang M-F, Chang H-T. 2012. Detection of carbohydrates using surface- complex. Chem Commun 47:12795–12797. assisted laser desorption/ionization mass spectrometry with HgTe Imura T, Kawamura D, Ishibashi Y, Morita T, Sato S, Fukuoka T, Kikkawa Y, nanostructures. Chem Sci 3:2147–2152. Kitamoto D. 2012. Low molecular weight gelators based on biosurfac- Huang S-X, Feng Z, Wang L, Galm U, Wendt-Pienkowski E, Yang D, Tao tants, cellobiose lipids by Cryptococcus humicola. J Oleo Sci 61:659–664. M, Coughlin JM, Duan Y, Shen B. 2012a. A designer bleomycin with Inamori K-I, Yoshida-Moriguchi T, Hara Y, Anderson ME, Yu L, Campbell significantly improved DNA cleavage activity. J Am Chem Soc KP. 2012. Dystroglycan function requires xylosyl- and glucuronyl- 134:13501–13509. transferase activities of LARGE. Science 335:93–96. Huang W, Giddens J, Fan S-Q, Toonstra C, Wang L-X. 2012b. Chemo- Inoue T, Iijima H, Tajiri M, Shinzaki S, Shiraishi E, Hiyama S, Mukai A, enzymatic glycoengineering of intact IgG antibodies for gain of Nakajima S, Iwatani H, Nishida T, Mizushima T, Yasui T, Isaka Y, functions. J Am Chem Soc 134:12308–12318. Kanto T, Tsujii M, Miyoshi E, Wada Y, Takehara T. 2012. Deficiency Huang Y-L, Tanaka T, Matsuo Y, Kouno I, Li D-P, Nonaka G-I. 2012c. Two of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a new phenolic glucosides and an ellagitannin from the leaves of novel biologic marker for Crohn’s disease. Inflamm Bowel Dis Castanopsis sclerophylla. Phytochem Lett 5:158–161. 18:1723–1734.

Mass Spectrometry Reviews DOI 10.1002/mas 137 & HARVEY

Ishibashi Y, Ikeda K, Sakaguchi K, Okino N, Taguchi R, Ito M. 2012. Quality Cronobacter sakazakii isolated from oil contaminated wastewater. control of fungus-specific glucosylceramide in Cryptococcus neofor- Carbohydr Polym 87:2320–2326. mans by endoglycoceramidase-related protein 1 (EGCrP1). J Biol Jain RM, Mody K, Mishra A, Jha B. 2012b. Physicochemical characteriza- Chem 287:368–381. tion of biosurfactant and its potential to remove oil from soil and cotton Ishihara T, Fukuda I, Morita A, Takinami Y, Okamoto H, Nishimura S-I, cloth. Carbohydr Polym 89:1110–1116. Numata Y. 2011. Development of quantitative plasma N-glycoproteo- Jaiswal N, Saraswat S, Ratnam M, Isailovic D. 2012. Analysis of folate mics using label-free 2-D LC-MALDI MS and its applicability for binding protein N-linked glycans by mass spectrometry. J Proteome biomarker discovery in hepatocellular carcinoma. J Proteomics Res 11:1551–1560. 74:2159–2168. Jakab Z, Fekete A, Csavas M, Borbas A, Liptak A, Antus S. 2012. Synthesis Ishino T, Economou NJ, McFadden K, Zaks-Zilberman M, Jost M, Baxter S, of a sulfonic acid mimetic of the sulfated Lewis A pentasaccharide. Contarino MR, Harrington AE, Loll PJ, Pasut G, Lievens S, Tavernier Carbohydr Res 350:90–93. J, Chaiken I. 2011. A protein engineering approach differentiates the Jang K-S, Baik JE, Han SH, Chung DK, Kim B-G. 2011. Multi-spectromet- functional importance of carbohydrate moieties of interleukin-5 ric analyses of lipoteichoic acids isolated from Lactobacillus planta- receptor a. Biochemistry 50:7546–7556. rum. Biochem Biophys Res Commun 407:823–830. Ishiwata A, Ito Y. 2011. Synthesis of docosasaccharide arabinan motif of Jang K, Miura K, Koyama Y, Takata T. 2012. Catalyst- and solvent-free click mycobacterial cell wall. J Am Chem Soc 133:2275–2291. synthesis of cyclodextrin-based polyrotaxanes exploiting a nitrile N- Ishiwata A, Sakurai A, Nishimiya Y, Tsuda S, Ito Y. 2011. Synthetic study oxide. Org Lett 14:3088–3091. and structural analysis of the antifreeze agent xylomannan from Upis Jankovic M. 2011. Glycans as biomarkers: Status and perspectives. J Med ceramboides. J Am Chem Soc 133:19524–19535. Biochem 30:213–223. Ishiwata A, Sakurai A, Ito Y. 2012. Accelerated O-glycosylation under Jantscher-Krenn E, Zherebtsov M, Nissan C, Goth K, Guner YS, Naidu N, frozen conditions and its application to the synthesis of complex Choudhury B, Grishin AV, Ford HR, Bode L. 2012. The human milk glycans. Trends Glycosci Glycotechnol 24:179–189. oligosaccharide disialyllacto-N-tetraose prevents necrotising enteroco- Ismail MN, Stone EL, Panico M, Lee SH, Luu Y, Ramirez K, Ho SB, Fukuda litis in neonatal rats. Gut 61:1417–1425. M, Marth JD, Haslam SM, Dell A. 2011. High-sensitivity O-glycomic Jaskolla TW, Karas M. 2011. Compelling evidence for lucky survivor and analysis of mice deficient in core 2 b1,6-N-acetylglucosaminyltransfer- gas phase protonation: The unified MALDI analyte protonation ases. Glycobiology 21:82–98. mechanism. J Am Soc Mass Spectrom 22:976–988. Ito E, Tominaga A, Waki H, Miseki K, Tomioka A, Nakajima K, Kakehi K, Jaskolla TW, Lehmann W-D, Karas M. 2008. 4-Chloro-alpha-cyanocin- Suzuki M, Taniguchi N, Suzuki A. 2012. Structural characterization of namic acid is an advanced, rationally designed MALDI matrix. Proc monosialo-, disialo- and trisialo-gangliosides by negative ion AP- Natl Acad Sci. USA 105:12200–12205. MALDI-QIT-TOF mass spectrometry with MSn switching. Neurochem Jassem AN, Zlosnik JEA, Henry DA, Hancock REW, Ernst RK, Speert DP. Res 37:1315–1324. 2011. In vitro susceptibility of Burkholderia vietnamiensis to amino- € Ivanova V, Dornyei A, Stefova M, Stafilov T, Vojnoski B, Kilar F, Mark L. glycosides. Antimicrob Agents Chemother 55:2256–2264. 2011. Rapid MALDI-TOF-MS detection of anthocyanins in wine and Jawhara S, Habib K, Maggiotto F, Pignede G, Vandekerckove P, Maes E, grape using different matrices. Food Anal Meth 4:108–115. Dubuquoy L, Fontaine T, Guerardel Y, Poulain D. 2012. Modulation of Iwasaki Y, Nakano Y, Mochizuki K, Nomoto M, Takahashi Y, Ito R, Saito K, intestinal inflammation by yeasts and cell wall extracts: Strain Nakazawa H. 2011. A new strategy for ionization enhancement by dependence and unexpected anti-inflammatory role of glucan fractions. derivatization for mass spectrometry. J Chrom B 879:1159–1165. PLoS One 7:e40648. Iwashkiw JA, Seper A, Weber BS, Scott NE, Vinogradov E, Stratilo C, Reiz Jayaraman A, Koh X, Li J, Raman R, Viswanathan K, Shriver Z, B, Cordwell SJ, Whittal R, Schild S, Feldman MF. 2012. Identification Sasisekharan R. 2012. Glycosylation at Asn91 of H1N1 haemagglutinin of a general O-linked protein glycosylation system in Acinetobacter affects binding to glycan receptors. Biochem J 444:429–435. baumannii and its role in virulence and biofilm formation. PLoS Pathog Jensen PH, Karlsson NG, Kolarich D, Packer NH. 2012. Structural analysis 8:e1002758. of N- and O-glycans released from glycoproteins. Nat Protocols Iwatani H, Inoue T, Wada Y, Nagasawa Y, Yamamoto R, Iijima H, Takehara 7:1299–1300. T, Imai E, Rakugi H, Isaka Y. 2012. Quantitative change of IgA hinge Jeong D, Piao J, Kwon C, Jung S. 2012a. Synthesis of oligomeric microbial O-glycan composition is a novel marker of therapeutic responses of cyclosophoraoses as novel complexation agents. Bull Korean Chem IgA nephropathy. Biochem Biophys Res Commun 428:339–342. Soc 33:2095–2098. Jackowski O, Bussiere A, Vanhaverbeke C, Baussanne I, Peyrin E, Mingeot- Jeong H-J, Kim Y-G, Yang Y-H, Kim B-G. 2012b. High-throughput quantitative Leclercq M-P, Decout J-L. 2012. Major increases of the reactivity and analysis of total N-glycans by matrix-assisted laser desorption/ionization selectivity in aminoglycoside O-alkylation due to the presence of time-of-flight mass spectrometry. Anal Chem 84:3453–3460. fluoride ions. Tetrahedron 68:737–746. Jervis AJ, Butler JA, Lawson AJ, Langdon R, Wren BW, Linton D. 2012. Jackson SN, Colsch B, Egan T, Lewis EK, Schultz JA, Woods AS. 2011. Characterization of the structurally diverse N-linked glycans of Gangliosides’ analysis by MALDI-ion mobility MS. Analyst 136:463– Campylobacter species. J Bacteriol 194:2355–2362. 466. Jiang B-P, Guo D-S, Liu Y. 2011a. Reversible and selective sensing of aniline € ~ Jager C, Ferrara C, Umana P, Zeck A, Regula JT, Koll H. 2012. vapor by perylene-bridged bis(cyclodextrins) assembly. J Org Chem Determination of antibody glycosylation by mass spectrometry. 76:6101–6107. Methods Mol Biol 901:195–208. Jiang Y, Li F, Zha D, Potgieter TI, Mitchell T, Moore R, Cukan M, Houston- Jahouh F, Hou S-j Kovac P, Banoub JH. 2011. Determination of the glycation Cummings NR, Nylen A, Drummond JE, McKelvey TW, d’Anjou M, sites of Bacillus anthracis neoglycoconjugate vaccine by MALDITOF/ Stadheim TA, Sethuraman N, Li H. 2011b. Purification process TOF-CID-MS/MS and LC-ESI-QqTOF-tandem mass spectrometry. J development of a recombinant monoclonal antibody expressed in Mass Spectrom 46:993–1003. glycoengineered Pichia pastoris. Protein Exp Purif 76:7–14. Jahouh F, Hou S-j Kovac P, Banoub JH. 2012. Determination of glycation Jiao L, Wan D, Zhang X, Li B, Zhao H, Liu S. 2012. Characterization and sites by tandem mass spectrometry in a synthetic lactose-bovine serum immunostimulating effects on murine peritoneal macrophages of albumin conjugate, a vaccine model prepared by dialkyl squarate oligosaccharide isolated from Panax ginseng C. A. Meyer. J Ethno- chemistry. Rapid Commun Mass Spectrom 26:749–758. pharmacol 114:490–496. Jain RM, Mody K, Mishra A, Jha B. 2012a. Isolation and structural Jimenez-Castells C, Defaus S, Moise A, Przbylski M, Andreu D, Gutierrez- characterization of biosurfactant produced by an alkaliphilic bacterium Gallego R. 2012. Surface-based and mass spectrometric approaches to

138 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

deciphering sugar-protein interactions in a galactose-specific aggluti- Kalmar L, Agoston K, Szurmai Z, Doncz€ oB,Ker} ekgyarto J. 2012. Synthesis nin. Anal Chem 84:6515–6520. of fully O-benzylated N-linked core pentasaccharide glycosyl azide. J Jmeian Y, Hammad LA, Mechref Y. 2012. Fast and efficient online release of Carbohydr Chem 31:203–219. N-glycans from glycoproteins facilitating liquid chromatography- Kaltashov IA, Bobst CE, Abzalimov RR, Wang G, Baykal B, Wang S. 2012. tandem mass spectrometry glycomic profiling. Anal Chem 84:8790– Advances and challenges in analytical characterization of biotechnolo- 8796. gy products: Mass spectrometry-based approaches to study properties Jo S, Song KC, Desaire H, MacKerell AD, Im W. 2011. Glycan Reader: and behavior of protein therapeutics. Biotechnol Adv 30:210–222. Automated sugar identification and simulation preparation for carbo- Kamani M, Mylvaganam M, Tian R, Rigat B, Binnington B, Lingwood C. hydrates and glycoproteins. J Comput Chem 32:3135–3141. 2011. Adamantyl glycosphingolipids provide a new approach to the Johannesen SA, Beeren SR, Blank D, Yang BY, Geyer R, Hindsgaul O. selective regulation of cellular glycosphingolipid metabolism. J Biol 2012. Glycan analysis via derivatization with a fluorogenic pyrylium Chem 286:21413–21426. dye. Carbohydr Res 352:94–100. Kameyama A, Matsuno Y-K. 2012. Recent advances in electrophoresis of John CM, Liu M, Phillips NJ, Yang Z, Funk CR, Zimmerman LI, Griffiss JM, mucins. Trends Glycosci Glycotechnol 24:137–151. Stein DC, Jarvis GA. 2012. Lack of lipid A pyrophosphorylation and Kamitakahara H, Murata-Hirai K, Tanaka Y. 2012. Synthesis of blockwise functional lptA reduces inflammation by Neisseria commensals. Infect alkylated tetrasaccharide-organic quantum dot complexes and their Immun 80:4014–4026. utilization for live cell labeling with low cytotoxicity. Cellulose Jones CJ, Beni S, Limtiaco JFK, Langeslay DJ, Larive CK. 2011. Heparin 19:171–187. characterization: Challenges and solutions. Annu Rev Anal Chem Kamiya Y, Yamamoto S, Chiba Y, Jigami Y, Kato K. 2011. Overexpression 4:439–465. of a homogeneous oligosaccharide with 13C labeling by genetically Jones MA, Ng BG, Bhide S, Chin E, Rhodenizer D, He P, Losfeld M-E, He engineered yeast strain. J Biomol NMR 50:397–401. M, Raymond K, Berry G, Freeze HH, Hegde MR. 2012a. DDOST Kanatani H, Kimura Y, Asanoma M, Nakamura A, Hirotsuka M, Asachi S. mutations identified by whole-exome sequencing are implicated in 2012. Absorption of the indigestible disaccharide, b-1,4-mannobiose, congenital disorders of glycosylation. Am J Hum Genet 90:363–368. from coconut by the rat portal vein. Biosci Biotechnol Biochem Jones MB, Nasirikenari M, Lugade AA, Thanavala Y, Lau JTY. 2012b. Anti- 76:575–577. inflammatory IgG production requires functional P1 promoter in b- Kanaya T, Schweizer F, Takeda T, Kiuchi F, Hada N. 2012. Synthetic studies galactoside a2,6-sialyltransferase 1 (ST6Gal-1) gene. J Biol Chem on glycosphingolipids from protostomia phyla: Synthesis of glyco- 287:15365–15370. sphingolipids and related carbohydrate moieties from the parasite Juengwatanatrakul T, Sritularak B, Amornnopparattanakul P, Tassanawat P, Schistosoma mansoni. Carbohydr Res 361:55–72. Putalun W, Tanaka H, Morimotoe S. 2011. Preparation of a specific Kandasamy J, Atia-Glikin D, Shulman E, Shapira K, Shavit M, Belakhov V, monoclonal antibody to asiaticoside for the development of an Baasov T. 2012. Increased selectivity toward cytoplasmic versus enzyme-linked immunosorbent assay. Analyst 136:1013–1017. mitochondrial ribosome confers improved efficiency of synthetic amino- Kabanova A, Margarit I, Berti F, Romano MR, Grandi G, Bensi G, Chiarot glycosides in fixing damaged genes: A strategy for treatment of genetic E, Proietti D, Swennen E, Cappelletti E, Fontani P, Casini D, Adamo R, diseases caused by nonsense mutations. J Med Chem 55:10630–10643. Pinto V, Skibinski D, Capo S, Buffi G, Gallotta M, Christ WJ, Campbell Kandiba L, Aitio O, Helin J, Guan Z, Permi P, Bamford DH, Eichler J, Roine AS, Pena J, Seeberger PH, Rappuoli R, Costantino P. 2011. Evaluation E. 2012. Diversity in prokaryotic glycosylation: An archaeal-derived of a Group A Streptococcus synthetic oligosaccharide as vaccine N-linked glycan contains legionaminic acid. Mol Microbiol 84:578– candidate. Vaccine 29:104–114. 593. Kabel MA, Yeoman CJ, Han Y, Dodd D, Abbas CA, de Bont JAM, Morrison Kanemaru M, Yamamoto K, Kadokawa J-I. 2012. Self-assembling properties M, Cann IKO, Mackie RI. 2011. Biochemical characterization and of 6-O-alkyltrehaloses under aqueous conditions. Carbohydr Res relative expression levels of multiple carbohydrate esterases of the 357:32–40. xylanolytic rumen bacterium Prevotella ruminicola 23 grown on an Kaneshiro K, Fukuyama Y, Iwamoto S, Sekiya S, Tanaka K. 2011. Highly ester-enriched substrate. Appl Environ Microbiol 77:5671–5681. sensitive MALDI analyses of glycans by a new aminoquinoline- Kadokawa J-I. 2011. Precision polysaccharide synthesis catalyzed by labeling method using 3-aminoquinoline/a-cyano-4-hydroxycinnamic enzymes. Chem Rev 111:4308–4345. acid liquid matrix. Anal Chem 83:3663–3667. Kajander T, Kuja-Panula J, Rauvala H, Goldman A. 2011. Crystal structure Kaneshiro K, Watanabe M, Terasawa K, Uchimura H, Fukuyama Y, Iwamoto and role of glycans and dimerization in folding of neuronal leucine- S, Sato T-A, Shimizu K, Tsujimoto G, Tanaka K. 2012. Rapid rich repeat protein AMIGO-1. J Mol Biol 413:1001–1015. quantitative profiling of N-glycan by the glycan-labeling method Kaji H, Shikanai T, Sasaki-Sawa A, Wen H, Fujita M, Suzuki Y, Sugahara D, using 3-aminoquinoline/a-cyano-4-hydroxycinnamic acid. Anal Chem Sawaki H, Yamauchi Y, Shinkawa T, Taoka M, Takahashi N, Isobe T, 84:7146–7151. Narimatsu H. 2012. Large-scale identification of N-glycosylated Kang J, Park K-M, Choi K-H, Park C-S, Kim G-E, Kim D, Cha J. 2011. proteins of mouse tissues and construction of a glycoprotein database, Molecular cloning and biochemical characterization of a heat-stable GlycoProtDB. J Proteome Res 11:4553–4566. type I pullulanase from Thermotoga neapolitana. Enzyme Microb Kajiura H, Misaki R, Fujiyamalow K, Seki T. 2011. Stable coexpression of Technol 48:260–266. two human sialylation enzymes in plant suspension-cultured tobacco Kang P, Madera M, Alley WRJ, Goldman R, Mechref Y, Novotny MV. 2011. cells. J Biosci Bioeng 111:471–477. Glycomic alterations in the highly-abundant and lesser-abundant blood Kajiura H, Okamoto T, Misaki R, Matsuura Y, Fujiyama K. 2012. serum protein fractions for patients diagnosed with hepatocellular Arabidopsis b1,2-xylosyltransferase: Substrate specificity and partici- carcinoma. Int J Mass Spectrom 305:185–198. pation in the plant-specific N-glycosylation pathway. J Biosci Bioeng Kang Y, Zhou L, Li X, Yuan J. 2011. b-Cyclodextrin-modified hybrid 113:48–54. magnetic nanoparticles for catalysis and adsorption. J Mater Chem Kakasi-Zsurka S, Todea A, But A, Paul C, Boeriu CG, Davidescu C, Nagy L, 21:3704–3710. Kuki A, Keki S, Peter F. 2011. Biocatalytic synthesis of new Kang J, Cui SW, Guo Q, Chen J, Wang Q, Phillips GO, Nikiforuk J. 2012a. copolymers from 3-hydroxybutyric acid and a carbohydrate lactone. J Structural investigation of a glycoprotein from gum ghatti. Carbohydr Mol Catal B Enzymatic 71:22–28. Polym 89:749–758. Kallberg K, Becker K, Bulow€ L. 2011. Application of a pH responsive Kang L-X, Chen X-M, Fu L, Ma L-X. 2012b. Recombinant expression of multimodal hydrophobic interaction chromatography medium for the chitosanase from Bacillus subtilis HD145 in Pichia pastoris. Carbo- analysis of glycosylated proteins. J Chrom A 1218:678–683. hydr Res 352:37–43.

Mass Spectrometry Reviews DOI 10.1002/mas 139 & HARVEY

Kanistanon D, Powell DA, Hajjar AM, Pelletier MR, Cohen IE, Way SS, the ability of lipid A to stimulate toll-like receptor 4. Biochem Biophys Skerrett SJ, Wang X, Raetz CRH, Ernst RK. 2012. Role of Francisella Res Commun 428:343–347. lipid A phosphate modification in virulence and long-term protective Keliher EJ, Yoo J, Nahrendorf M, Lewis JS, Marinelli B, Newton A, Pittet immune responses. Infect Immun 80:943–951. MJ, Weissleder R. 2011. 89Zr-Labeled dextran nanoparticles allow in Kano K, Chimoto S, Tamaki M, Itoh Y, Kitagishi H. 2012. Supramolecular vivo macrophage imaging. Bioconj Chem 22:2383–2389. dioxygen receptors composed of an anionic water-soluble porphina- Kempe K, Weber C, Babiuch K, Gottschaldt M, Hoogenboom R, toiron(II) and cyclodextrin dimers. Dalton Trans 41:453–461. Schubert US. 2011. Responsive glyco-poly(2-oxazoline)s: Synthesis, Kao P-F, Wang S-H, Hung W-T, Liao Y-H, Lin C-M, Wen-Bin Y. cloud point tuning, and lectin binding. Biomacromolecules 12:2591– 2012. Structural characterization and antioxidative activity of low- 2600. molecular-weights beta-1,3-glucan fromthe residue of extracted Kendrick E. 1963. A mass scale based on CH2 ¼ 14.0000 for high resolution Ganoderma lucidum fruiting bodies. J Biomed Biotechnol. Article ID mass spectrometry of organic compounds. Anal Chem 35:2146–2154. 673764. Kenny D, Hayes CA, Jin C, Karlsson NG. 2011. Perspective and review of Karsten CM, Pandey MK, Figge J, Kilchenstein R, Taylor PR, Rosas M, mass spectrometric based sulfoglycomics of N-linked and O-linked McDonald JU, Orr SJ, Berger M, Petzold D, Blanchard V, Winkler A, oligosaccharides. Curr Proteomics 8:278–296. Hess C, Reid DM, Majoul IV, Strait RT, Harris NL, Kohl€ G, Wex E, Ludwig R, Zillikens D, Nimmerjahn F, Finkelman FD, Brown GD, Kerekgyarto J, Kalmar L, Szurmai Z, Hegyi O, Toth GK. 2012. Synthesis Ehlers M, Kohl€ J. 2012. Anti-inflammatory activity of IgG1 mediated of N-glycopeptides by convergent assembly. Int J Peptide Res Ther by Fc galactosylation and association of FcgRIIB and dectin-1. Nat 18:1–5. Med 18:1401–1406. Keys TG, Freiberger F, Ehrit J, Krueger J, Eggers K, Buettner FFR, Gerardy- Kasai HF, Saito N, Honda T. 2011. Structural features of polyacylated Schahn R. 2012. A universal fluorescent acceptor for high-performance anthocyanins using matrix-assisted laser desorption/ionization and liquid chromatography analysis of pro- and eukaryotic polysialyltrans- electrospray ionization time-of-flight mass spectrometry. Rapid Com- ferases. Anal Biochem 427:107–115. mun Mass Spectrom 25:1051–1060. Khan SN, Kim A, Grubbs RH, Kwon Y-U. 2012. Cross metathesis assisted Kaspar S, Peukert M, Svatos A, Matros A, Mock H-P. 2011. MALDI- solid-phase synthesis of glycopeptoids. Org Lett 14:2952–2955. imaging mass spectrometry—An emerging technique in plant biology. Kilar A, Dornyei€ A, Bui A, Szabo Z, Kocsis B, Kilar F. 2011. Structural Proteomics 11:1840–1850. variability of endotoxins from R-type isogenic mutants of Shigella Kataev VE, Strobykina IY, Andreeva OV, Garifullin BF, Sharipova RR, sonnei. J Mass Spectrom 46:61–70. Mironov VF, Chestnova RV. 2011. Synthesis and antituberculosis Kim EH, Misek DE. 2011. Glycoproteomics-based identification of cancer activity of derivatives of Stevia rebaudiana glycoside steviolbioside biomarkers. Int J Proteomics 60: Article 601937. and diterpenoid isosteviol containing hydrazone, hydrazide, and pyridinoyl moieties. Russ J Bioorg Chem 37:483–491. Kim J-H, Wang R, Lee W-H, Park C-S, Lee S, Yoo S-H. 2011a. One-pot synthesis of cycloamyloses from sucrose by dual enzyme treatment: Katagiri YU, Sato B, Yamatoya K, Taki T, Goto-Inoue N, Setou M, Okita H, combined reaction of amylosucrase and 4-a-glucanotransferase. J Fujimoto J, Ito C, Toshimori K, Kiyokawa N. 2011. GalNAcb1,3- Agric Food Chem 59:5044–5051. linked paragloboside carries the epitope of a sperm maturation-related Kim KY, Kim KR, Kang DG, Jang SY. 2011b. Expression of b-1,4- glycoprotein that is recognized by the monoclonal antibody MC121. b N Biochem Biophys Res Commun 406:326–331. galactosyltransferase and suppression of - -acetylglucosaminidase to aid synthesis of complex N-glycans in insect Drosophila S2 cells. J Katayama H, Asahina Y, Hojo H. 2011. Chemical synthesis of the S-linked Biotechnol 153:145–152. glycopeptide, sublancin. J Peptide Sci 17:818–821. Kim SK, Kim YC, Lee S, Kim JC, Yun MY, Kim IS. 2011c. Insecticidal Kato A, Hayashi E, Miyauchi S, Adachi I, Imahori T, Natori Y, Yoshimura Y, activity of rhamnolipid isolated from Pseudomonas sp. EP-3 against green Nash RJ, Shimaoka H, Nakagome I, Koseki J, Hirono S, Takahata H. peach aphid (Myzus persicae). J Agric Food Chem 59:934–938. 2012. a-1-C-Butyl-1,4-dideoxy-1,4-imino-L-arabinitol as a second- generation iminosugar-based oral a-glucosidase inhibitor for improv- Kim Y-C, Udeshi ND, Balsbaugh JL, Shabanowitz J, Hunt DF, Olszewski ing postprandial hyperglycemia. J Med Chem 55:10347–10362. NE. 2011d. O-GlcNAcylation of the Plum pox virus capsid protein O Kaufmann S, Ilg K, Mashaghi A, Textor M, Priem B, Aebi M, Reimhult E. catalyzed by SECRET AGENT: Characterization of -GlcNAc sites 2012. Supported lipopolysaccharide bilayers. Langmiur 28:12199–12208. by electron transfer dissociation mass spectrometry. Amino Acids 40:869–876. Kaup M, Saul VV, Lusch A, Dorsing€ J, Blanchard V, Tauber R, Berger M. 2011. Construction and analysis of a novel peptide tag containing an Kim Y-K, Na H-K, Kwack S-J, Ryoo S-R, Lee Y, Hong S, Hong S, Jeong Y, unnatural N-glycosylation site. FEBS Lett 585:2372–2376. Min D-H. 2011e. Synergistic effect of graphene oxide/MWCNT films in laser desorption/ionization mass spectrometry of small molecules Kauscher U, Ravoo BJ. 2012. Mannose-decorated cyclodextrin vesicles: The and tissue imaging. ACS Nano 5:4550–4561. interplay of multivalency and surface density in lectin-carbohydrate recognition. Beilstein J Org Chem 8:1543–1551. Kim Y-K, Min D-H. 2012a. Fabrication of alternating multilayer films of Kavita K, Mishra A, Jha B. 2011. Isolation and physico-chemical characteri- graphene oxide and carbon nanotube and its application in mechanistic sation of extracellular polymeric substances produced by the marine study of laser desorption/ionization of small molecules. ACS Appl bacterium Vibrio parahaemolyticus. Biofouling 27:309–317. Mater Interfaces 4:2088–2095. Kawagoe N, Kasori Y, Hasegawa T. 2011. Highly C6-selective and Kim Y-K, Min D-H. 2012b. Preparation of the hybrid film of poly(allylamine quantitative modification of cellulose: Nucleoside-appended celluloses hydrochloride)-functionalized graphene oxide and gold nanoparticle to solubilize single walled carbon nanotubes. Cellulose 18:83–93. and its application for laser-induced desorption/ionization of small molecules. Langmuir 28:4453–4458. Kawasaki K. 2012. Complexity of lipopolysaccharide modifications in Salmonella enterica: Its effects on endotoxin activity, membrane Kim B-J, Yi S-Y, Shim T-S, Do SY, Yu H-K, Park Y-G, Kook Y-H, Kim B-J. permeability, and resistance to antimicrobial peptides. Food Res Int 2012a. Discovery of a novel hsp65 genotype within Mycobacterium 45:493–501. massiliense associated with the rough colony morphology. PLoS One 7:e38420. Kawasaki H, Ozawa T, Hisatomi H, Arakawa R. 2012a. Platinum vapor deposition surface-assisted laser desorption/ionization for imaging Kim CS, Seo JH, Cha HJ. 2012b. Functional interaction analysis of GM1- mass spectrometry of small molecules. Rapid Commun Mass Spectrom related carbohydrates and Vibrio cholerae toxins using carbohydrate 26:1849–1858. microarray. Anal Chem 84:6884–6890. Kawasaki K, Teramoto M, Tatsui R, Amamoto S. 2012b. Lipid A 3’-O- Kim D-H, Jang JG, Le HT, Kim JY, Lim CW, Kim TW. 2012c. 6- deacylation by Salmonella outer membrane enzyme LpxR modulates Hydroxymethyltriazolyl-6-deoxy-b-cyclodextrin: a highly water

140 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

soluble and structurally well-defined b-cyclodextrin click cluster. Koizumi A, Yamano K, Tsuchiya T, Schweizer F, Kiuchi F, Hada N. 2012. Tetrahedron Lett 53:5791–5795. Synthesis, antigenicity against human sera and structure-activity Kim E-M, Kim J, Seo J-H, Park J-S, Kim D-H, Kim B-G. 2012d. relationships of carbohydrate moieties from Toxocara larvae and their Identification and characterization of the Rhizobium sp. Strain GIN611 analogues. Molecules 17:9023–9042. glycoside oxidoreductase resulting in the deglycosylation of ginseno- Kojima H, Shimizu T, Sugita M, Itonori S, Fujita N, Ito M. 2011. sides. Appl Environ Microbiol 78:242–249. Biochemical studies on sphingolipids of Artemia franciscana: Novel Kim G-E, Kang H-K, Seo E-S, Jung S-H, Park J-S, Kim D-H, Kim D-W, neutral glycosphingolipids. J Lipid Res 52:308–317. Ahn S-A, Sunwoo C, Kim D. 2012e. Glucosylation of the flavonoid, Kolarich D, Lepenies B, Seeberger PH. 2012. Glycomics, glycoproteomics astragalin by Leuconostoc mesenteroides B- 512FMCM dextransu- and the immune system. Curr Opin Chem Biol 16:214–220. crase acceptor reactions and characterization of the products. Enzyme Kolender AA, Arce SM, Varela O. 2011. Synthesis and characterization of Microb Technol 50:50–56. poly-O-methyl-[n]-polyurethane from a D-glucamine-based monomer. Kim H, Kim K, Choi JM, Tahir MN, Cho E, Choi Y, Lee I-S, Jung S. 2012f. Carbohydr Res 346:1398–1405. Solubilization of pyrimethamine, antibacterial drug, by low-molecular- Koliwer-Brandl H, Gbem TT, Waespy M, Reichert O, Mandel P, Drebitz E, weight succinoglycan dimers isolated from Shinorhizobium meliloti. Dietz F, Kelm S. 2009. 2011. Biochemical characterization of trans- Bull Korean Chem Soc 33:2731–2736. sialidase TS1 variants from Trypanosoma congolense. BMC Biochem Kim Y-S, Kim S-H, Kang J-G, Ko J-H. 2012g. Expression level and glycan 12: Article39. dynamics determine the net effects of timp-1 on cancer progression. Kolli VSK, Orlando R. 1996. A new matrix for matrix-assisted laser BMB Reports 45:623–628. desorption/ionization on magnetic sector instruments with point Kimura K, Tanaka I, Nishimura S-I, Miyoshi R, Miyoshi T, Watanabe Y. detectors. Rapid Commun Mass Spectrom 10:923–926. 2012a. Further examination of polysaccharides causing membrane Kondo A, Østerlund EC. 2011. Determination of the glycostructure in b2- fouling in membrane bioreactors (MBRs): Application of lectin affinity glycoprotein I by liquid chromatography/electrospray ionization chromatography and MALDI-TOF/MS. Water Res 46:5725–5734. tandem mass spectrometry. J Mass Spectrom Soc Japan 59:107–116. Kimura T, Nakajima T, Kamijo Y, Tanaka N, Wang L, Hara A, Sugiyama E, Kondo S, Yagi H, Kamiya Y, Ito A, Kuhara M, Kudoh A, Takahashi N, Kato Tanaka E, Gonzalez FJ, Aoyama T. 2012b. Hepatic cerebroside K. 2012. N-Glycosylation profiles of chicken immunoglobulin Y sulfotransferase is induced by PPARa activation in mice. PPAR Res glycoproteins expressed by different production vehicles. J Glycom Article 174932. Lipidom. Article S5. Kireeva GK, Zhorin VA, Razumovskii SD, Varfolomeev SD. 2011. Mass Kong F-L, Cheng W, Chen J, Liang Y. 2011. D-Ribose glycates b2- spectrometry of the products of the mechanochemical degradation of microglobulin to form aggregates with high cytotoxicity through a amylose macromolecules. Russ J Phys Chem A 85:1187–1189. ROS-mediated pathway. Chem Biol Interact 194:69–78. Kirmizibekmez H, Ariburnu E, Masullo M, Festa M, Capasso A, Yesilada E, Konishi M-A, Fukuoka T, Shimane Y, Mori K, Nagano Y, Ohta Y, Kitamoto Piacente S. 2012. Iridoid, phenylethanoid and flavonoid glycosides D, Hatada Y. 2011. Biochemical synthesis of novel self-assembling from Sideritis trojana. Fitoterapia 83:130–136. glycolipids from ricinoleic acid by a recombinant a-glucosidase from Kitagishi H, Kashiwa K, Kano K. 2012. Functionalization of a protein surface Geobacillus sp. Biotechnol Lett 33:139–145. with per-O-methylated b- cyclodextrin. Biopolymers 97:11–20. Konishi T, Ishii T. 2012. The origin and functions of arabinofuranosyl Kitamura A, Matsui K, Konoki K, Matsumori N, Murata M, Kawakami T, residues in plant cell walls. Trends Glycosci Glycotechnol 24:13–23. Aimoto S. 2011. Lysine proximity significantly affects glycation of lysine- Konishi Y, Aoki-Kinoshita KF. 2012. The GlycomeAtlas tool for visualizing containing collagen model peptides. Bioorg Med Chem 19:2125–2129. and querying glycome data. Bioinformatics 28:2849–2850. Klein KA, Fukuto HS, Pelletier M, Romanov G, Grabenstein JP, Palmer LE, Korochkina MG, Sharipova RR, Strobykina IY, Lantsova AD, Voloshina Ernst R, Bliska JB. 2012. A transposon site hybridization screen AD, Kulik NV, Zobov VV, Kataev VE, Mironov VF. 2011. Synthesis identifies galU and wecBC as important for survival of Yersinia pestis and antimicrobial and antifungal activity of derivatives of the in murine macrophages. J Bacteriol 194:653–662. diterpenoid isosteviol and the glycoside steviolbioside containing Knochenmuss R, Zhigilei LV. 2012. What determines MALDI ion yields?: A onium nitrogen atoms. Pharm Chem J 44:597–600. molecular dynamics study of ion loss mechanisms. Anal Biochem Kosk O, Garajova S, MatulovaM,Rehulka P, Stratilova E, Farkas V. 2011. 402:2511–2519. Effect of the label of oligosaccharide acceptors on the kinetic Ko BJ, Brodbelt JS. 2011. 193 nm ultraviolet photodissociation of parameters of nasturtium seed xyloglucan endotransglycosylase deprotonated sialylated oligosaccharides. Anal Chem 83:8192–8200. (XET). Carbohydr Res 346:357–361. Ko Y-C, Tsai W-H, Wang P-W, Wu I-L, Lin S-Y, Chen Y-L, Chen J-Y, Lin S- Koulakiotis NS, Pittenauer E, Halabalaki M, Tsarbopoulos A, Allmaier G. F. 2012. Suppressive regulation of KSHV RTA with O-GlcNAcylation. 2012. Comparison of different tandem mass spectrometric techniques J Biomed Sci 19. Article12. (ESI-IT, ESI- and IP-MALDI- QRTOF and vMALDI-TOF/RTOF) for Kobayashi H, Endo T, Ogawa N, Nagase H, Iwata M, Ueda H. 2011a. the analysis of crocins and picrocrocin from the stigmas of Crocus Evaluation of the interaction between b-cyclodextrin and psychotropic sativus L. Rapid Commun Mass Spectrom 26:670–678. drugs by surface plasmon resonance assay with a Biacore(r) system. J Kowalczyk W, Mascaraque A, Sanchez-Navarro M, Rojo J, Andreu D. 2012. Pharm Biomed Anal 54:258–263. Convergent synthesis of glycodendropeptides by click chemistry Kobayashi M, Mitoma J, Hoshino H, Yu S-Y, Shimojo Y, Suzawa K, approaches. Eur J Org Chem 4565–4573. Khoo K-H, Fukuda M, Nakayama J. 2011b. Prominent expression Kozak RP, Royle L, Gardner RA, Fernandes DL, Wuhrer M. 2012. of sialyl Lewis X-capped core 2-branched O-glycans on high Suppression of peeling during the release of O-glycans by hydrazinol- endothelial venule-like vessels in gastric MALT lymphoma. J Pathol ysis. Anal Biochem 423:119–128. 224:67–77. Kralj S, Grijpstra P, van Leeuwen SS, Leemhuis H, Dobruchowska JM, van Kodama T, Togawa T, Tsukimura T, Kawashima I, Matsuoka K, Kitakaze K, der Kaaij RM, Malik A, Oetari A, Kamerling JP, Dijkhuizen L. 2011. Tsuji D, Itoh K, Ishida Y-i Suzuki M, Suzuki T, Sakuraba H. 2011. 4,6-a-Glucanotransferase, a novel enzyme that structurally and func- Lyso-GM2 ganglioside: A possible biomarker of Tay-Sachs disease tionally provides an evolutionary link between glycoside hydrolase and Sandhoff disease. PLoS One 6:e29074. enzyme families 13 and 70. Appl Environ Microbiol 77:8154–8163. Koizumi A, Yamano K, Schweizer F, Takeda T, Kiuchi F, Hada N. 2011. Krause B, Seifert S, Panne U, Kneipp J, Weidner SM. 2012. Matrix-assisted Synthesis of the carbohydrate moiety from the parasite Echinococcus laser desorption/ionization mass spectrometric investigation of pollen multilocularis and their antigenicity against human sera. Eur J Med and their classification by multivariate statistic. Rapid Commun Mass Chem 46:1768–1778. Spectrom 26:1032–1038.

Mass Spectrometry Reviews DOI 10.1002/mas 141 & HARVEY

Krishna S, Ray A, Dubey SK, Larrouy-Maumus G, Chalut C, Castanier R, Kurakake M, Ito Y, Komaki T. 2011. Synthesis of sugar fatty acid esters Noguera A, Gilleron M, Puzo G, Vercellone A, Nampoothiri KM, using a b-xylosidase from Aspergillus awamori for transxylosylation. Nigou J. 2011. Lipoglycans contribute to innate immune detection of Biotechnol Lett 33:2453–2456. mycobacteria. PLoS One 6:e28476. Kurtovic T, Brgles M, Leonardi A, Balija ML, Krizaj I, Allmaier G, Krishnan N, Malaga W, Constant P, Caws M, Chau TTH, Salmons J, Lan Marchetti-Deschmann M, Halassy B. 2011. Ammodytagin, a hetero- NTN, Bang ND, Daffe M, Young DB, Robertson BD, Guilhot C, dimeric metalloproteinase from Vipera ammodytes ammodytes venom Thwaites GE. 2011. Mycobacterium tuberculosis lineage influences with strong hemorrhagic activity. Toxicon 58:570–582. innate immune response and virulence and is associated with distinct Kuru E, Hughes HV, Brown PJ, Hall E, Tekkam S, Cava F, de Pedro MA, cell envelope lipid profiles. PLoS One 6:e23870. Brun YV, Van Nieuwenhze MS. 2012. In situ probing of newly Krishnan R, Rakhi AM, Gopidas KR. 2012. Study of b-cyclodextrin- synthesized peptidoglycan in live bacteria with fluorescent D-amino pyromellitic diimide complexation. Conformational analysis of binary acids. Angew Chem Int Ed 51:12519–12523. and ternary complex structures by induced circular dichroism and 2D Kutkowska J, Turska-Szewczuk A, Janczarek M, Paduch R, Kaminska T, NMR spectroscopies. J Phys Chem C 116:25004–25014. Urbanik-Sypniewska T. 2011. Biological activity of (lipo) polysacchar- Kronewitter SR, De Leoz MLA, Strum JS, An HJ, Dimapasoc LM, Guerrero ides of the exopolysaccharide-deficient mutant Rt120 derived from A, Miyamoto S, Lebrilla CB, Leiserowitz GS. 2012. The glycolyzer: Rhizobium leguminosarum bv. trifolii strain TA1. Biochemistry Automated glycan annotation software for high performance mass (Moscow) 76:840–850. spectrometry and its application to ovarian cancer glycan biomarker Kwon C, Jung S. 2011a. pH-Dependent inclusion complexation of highly discovery. Proteomics 12:2523–2538. succinylated cyclosophoraoses with 4’- hydroxyflavanone. Bull Kore- Kubler-Kielb J. 2011. Conjugation of LPS-derived oligosaccharides to an Chem Soc 32:2791–2794. proteins using oxime chemistry. Methods Mol Biol 751:317–327. Kwon C, Jung S. 2011b. Stereoisomeric separation of some flavanones Kubler- Kielb J, Vinogradov E, Lagerga˚rd T, Ginzberg A, King JD, Preston using highly succinate-substituted a- cyclosophoro-octadecaoses as A, Maskell DJ, Pozsgay V, Keith JM, Robbins JB, Schneerson R. 2011. chiral additives in capillary electrophoresis. Carbohydr Res 346:133– Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica 139. induce bactericidal antibodies, an addition to pertussis vaccine. Proc Kwon C, Jeong D, Jung S. 2011a. Chiral separation of catechin by capillary Natl Acad Sci USA 108:4087–4092. electrophoresis with a- cyclosophorooctadecaose isolated from Rho- Kueger S, Steinhauser D, Willmitzer L, Giavalisco P. 2012. High-resolution dobacter sphaeroides as chiral selectors. Bull Korean Chem Soc plant metabolomics: from mass spectral features to metabolites and 32:1361–1364. from whole-cell analysis to subcellular metabolite distributions. Plant J Kwon C, Lee S, Jung S. 2011b. Matrix-assisted laser desorption/ionization 70:39–50. time-of-flight mass spectrometric behavior of succinoglycan mono- Kuhnel€ S, Westphal Y, Hinz SWA, Schols HA, Gruppen H. 2011. Mode of mers, dimers, and trimers isolated from Sinorhizobium meliloti 1021. action of Chrysosporium lucknowense C1 a-L-arabinohydrolases. Carbohydr Res 346:2308–2314. Bioresource Technol 102:1636–1643. Kwon Y, Cho E, Lee I-S, Jung S. 2011c. Synthesis and characterization of Kukushkin NV, Alonzi DS, Dwek RA, Butters TD. 2011. Demonstration that butyryl cyclosophoraose, and its inclusion complexation behavior for endoplasmic reticulum-associated degradation of glycoproteins can occur some flavonoids. Bull Korean Chem Soc 32:2779–2782. downstream of processing by endomannosidase. Biochem J 438:133–142. Kwon C, Kang YJ, Jeon S, Jung S, Hong SY, Kang S. 2012a. Development Kulkarni AR, Pattathil S, Hahn MG, York WS, O’Neill MA. 2012. of protein-cage-based delivery nanoplatforms by polyvalently display- Comparison of arabinoxylan structure in bioenergy and model grasses. ing b-cyclodextrins on the surface of ferritins through copper(I)- Indust Biotechnol 8:222–229. catalyzed azide/alkyne cycloaddition. Macromol Biosci 12:1452– Kulkarni AR, Pena~ MJ, Avci U, Mazumder K, Urbanowicz BR, Pattathil S, 1458. Yin Y, O’Neill MA, Roberts AW, Hahn MG, Xu Y, Darvill AG, York Kwon C, Choi Y, Jeong D, Kim JG, Choi JM, Chun S, Park S, Jung S. 2012b. WS. 2012. The ability of land plants to synthesize glucuronoxylans Inclusion complexation of naproxen with cyclosophoraoses and predates the evolution of tracheophytes. Glycobiology 22:439–451. succinylated cyclosophoraoses in different pH environments. J Incl Kumar V, Satyanarayana T. 2011. Applicability of thermo-alkali- stable and Phenom Macrocyclic Chem 74:325–333. cellulase-free xylanase from a novel thermo-halo-alkaliphilic Bacillus Kwon SJ, Lee KB, Solakyildirim K, Masuko S, Ly M, Zhang F, Li L, halodurans in producing xylooligosaccharides. Biotechnol Lett Dordick JS, Linhardt RJ. 2012c. Signal amplification by Glyco-qPCR 33:2279–2285. for ultrasensitive detection of carbohydrates: Applications in glycobi- Kumar AP, Nandini CD, Salimath PV. 2011a. Structural characterization of ology. Angew Chem Int Ed 51:11800–11804. N-linked oligosaccharides of laminin from rat kidney: Changes during Lahaye M, Quemener B, Causse M, Seymour GB. 2012a. Hemicellulose fine diabetes and modulation by dietary fiber and butyric acid. FEBS J structure is affected differently during ripening of tomato lines with 278:143–155. contrasted texture. Int J Biol Macromol 51:462–470. Kumar S, Xue L, Arya DP. 2011b. Neomycin-neomycin dimer: An all- Lahaye M, Falourd X, Quemener B, Ralet MC, Howad W, Dirlewanger E, carbohydrate scaffold with high affinity for AT-rich DNA duplexes. J Arus P. 2012b. Cell wall polysaccharide chemistry of peach genotypes Am Chem Soc 122:7361–7375. with contrasted textures and other fruit traits. J Agric Food Chem Kumar R, Whitfield DM. 2012. Could diastereoselectivity in the presence of O-2 60:6594–6605. chiral nonparticipating groups be an indicator of glycopyranosyl oxacarbe- Lai Y-H, So P-K, Lo SC-L, Ng EWY, Poon TCW, Yao Z-P. 2012. Rapid nium ions in glycosylation reactions?. J Org Chem 77:3724–3739. differentiation of Panax ginseng and Panax quinquefolius by matrix- Kuo C-Y, Liao K-S, Liu Y-C, Yang W-B. 2011. Bis-indole derivatives for assisted laser desorption/ionization mass spectrometry. Anal Chim polysaccharide compositional analysis and chiral resolution of D-, L- Acta 753:73–81. monosaccharides by ligand exchange capillary electrophoresis using Lakshminarayanan V, Thompson P, Wolfert MA, Buskas T, Bradley JM, borate-cyclodextrin as a chiral selector. Molecules 16:1682–1694. Pathangey LB, Madsen CS, Cohen PA, Gendler SJ, Boons G-J. 2012. Kuo C-W, Wu I-L, Hsiao H-H, Khoo K-H. 2012a. Rapid glycopeptide Immune recognition of tumor- associated mucin MUC1 is achieved by enrichment and N-glycosylation site mapping strategies based on a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine. Proc amine-functionalized magnetic nanoparticles. Anal Bioanal Chem Natl Acad Sci USA 109:261–266. 402:2765–2776. Lam MPY, Lau E, Liu X, Li J, Chu IK. 2012. Sample preparation for Kuo T-Y, Huang C-L, Yang J-M, Huang W-J, Huang N-K, Chen Y-W, Lin R- glycoproteins. In: Pawliszyn J, editor. Comprehensive sampling and J, Yang Y-C. 2012b. The role of ribosylated-BSA in regulating PC12 sample preparation analytical techniques for scientists. Amsterdam: cell viability. Cell Biol Toxicol 28:255–267. Elsevier. pp. 307–322.

142 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Lampropoulou M, Yannakopoulou K. 2011. Synthesis and characterisation Lecorche P, Walrant A, Burlina F, Dutot L, Sagan S, Mallet J-M, Desbat B, of novel glycoclusters based on cell penetrating heptakis(6-amino- Chassaing G, Alves ID, Lavielle S. 2012. Cellular uptake and ethylamino-6-deoxy)-b- cyclodextrin. J Incl Phenom Macrocyclic biophysical properties of galactose and/or tryptophan containing cell- Chem 70:345–352. penetrating peptides. Biochim Biophys Acta 1818:448–457. ̊ Landberg E, Astrom€ E, Ka˚gedal B, Pa˚hlsson P. 2012. Disialo-trisialo Lee B-S, Lasanthi GD, Jayathilaka P, Huang J-S, Vida LN, Honig GR, Gupta bridging of transferrin is due to increased branching and fucosylation S. 2011a. Analyses of in vitro nonenzymatic glycation of normal and of the carbohydrate moiety. Clin Chim Acta 414:58–64. variant hemoglobins by MALDI-TOF mass spectrometry. J Biomol Laparra JM, Corzo-Martinez M, Villamiel M, Moreno FJ, Sanz Y. 2011. Tech 22:90–94. Maillard-type glycoconjugates from dairy proteins inhibit adhesion of Lee C-L, Chiu PCN, Pang P-C, Chu IK, Lee K-F, Koistinen R, Koistinen H, Escherichia coli to mucin. Food Chem 129:1435–1443. Sepp€al€a M, Morris HR, Tissot B, Panico M, Dell A, Yeung WSB. Lapolla A, Mosca A, Fedele D. 2011a. The general use of glycated 2011b. Glycosylation failure extends to glycoproteins in gestational haemoglobin for the diagnosis of diabetes and other categories of glucose diabetes mellitus. Evidence from reduced a2-6 sialylation and intolerance: Still a long way to go. Nutr Metab Cardiovas 21:467–475. impaired immunomodulatory activities of pregnancy- related glycode- Lapolla A, Porcu S, Traldi P. 2011b. Some views on proteomics in diabetes. lin-A. Diabetes 60:909–917. Clin Chem Lab Med 49:943–957. Lee C, Teng Q, Zhong R, Ye Z-H. 2011c. Molecular dissection of Larrouy-Maumus G, Skovierov a H, Dhouib R, Angala SK, Zuberogoitia S, xylan biosynthesis during wood formation in poplar. Mol Plant 4:730– Pham H, Villela AD, Mikusova K, Noguera A, Gilleron M, Valentnova 747. L, Kordulakova J, Brennan PJ, Puzo G, Nigou J, Jackson M. 2012. A Lee H, An HJ, Lerno LAJ, German JB, Lebrilla CB. 2011d. Rapid profiling small multidrug resistance-like transporter involved in the arabinosyla- of bovine and human milk gangliosides by matrix-assisted laser tion of arabinogalactan and lipoarabinomannan in mycobacteria. J Biol desorption/ionization Fourier transform ion cyclotron resonance mass Chem 287:39933–39941. spectrometry. Int J Mass Spectrom 305:138–150. Larsbrink J, Izumi A, Ibatullin FM, Nakhai A, Gilbert HJ, Davies GJ, Lee JH, Choi HS, Nasr KA, Ha M, Kim Y, Frangioni JV. 2011e. High- Brumer H. 2011. Structural and enzymatic characterization of a throughput small molecule identification using MALDI-TOF and a glycoside hydrolase family 31 a-xylosidase from Cellvibrio japonicus nanolayered substrate. Anal Chem 83:5283–5289. involved in xyloglucan saccharification. Biochem J 436:567–580. Lee S-E, Seo H-B, Kim H-J, Yeon J-H, Jung K-H. 2011f. Galactooligosac- LastovickovaM,Smetalova D, Bobalova J. 2011. The combination of lectin charide synthesis by active b-galactosidase inclusion bodies- contain- affinity chromatography, gel electrophoresis and mass spectrometry in ing Escherichia coli cells. J Microbiol Biotechnol 21:1151–1158. the study of plant glycoproteome: Preliminary insights. Chromatogra- Lee G, Azadi P. 2012. Peptide mapping and glycoanalysis of cancer cell- phia 73:S113–S122. expressed glycoproteins CA215 recognized by RP215 monoclonal Lattova E, Bartusik D, Spicer V, Jellusova J, Perreault H, Tomanek B. 2011. antibody. J Carbohydr Chem 31:10–30. Alterations in glycopeptides associated with herceptin treatment of Lee WS, Kim W, Kim K-T, Chung S-K. 2011g. Mitochondrial affinity of human breast carcinoma MCF-7 and T-lymphoblastoid cells. Mol Cell guanidine-rich molecular transporters built on monosaccharide scaf- Proteomics 10:M111.007765. folds: Stereochemistry and lipophilicity. Bull Korean Chem Soc Laurent N, Haddoub R, Voglmeir J, Flitsch SL. 2012. MALDI-ToF MS 32:2286–2300. analysis of glycosyltransferase activities on gold surface arrays. Lee C, Zhong R, Ye Z-H. 2012a. Arabidopsis family GT43 members are Methods Mol Biol 808:269–284. xylan xylosyltransferases required for the elongation of the xylan Laurino P, Kikkeri R, Seeberger PH. 2011. Continuous-flow reactor-based backbone. Plant Cell Physiol 53:135–143. synthesis of carbohydrate and dihydrolipoic acid- capped quantum Lee C, Zhong R, Ye Z-H. 2012b. Biochemical characterization of xylan dots. Nat Protocols 6:1210–1220. xylosyltransferases involved in wood formation in poplar. Plant Lavanant H, Loutelier-Bourhis C. 2012. Use of procaine and procainamide Signaling Behav 7:332–337. as derivatizing co-matrices for the analysis of oligosaccharides by Lee C, Teng Q, Zhong R, Ye Z-H. 2012c. Arabidopsis GUX proteins are matrix-assisted laser desorption/ionization time-of-flight mass spec- glucuronyltransferases responsible for the addition of glucuronic acid trometry. Rapid Commun Mass Spectrom 26:1311–1319. side chains onto xylan. Plant Cell Physiol 53:1204–1216. Layre E, Cala-De Paepe D, Larrouy-Maumus G, Vaubourgeix J, Mundayoor Lee C, Teng Q, Zhong R, Yuan Y, Haghighat M, Ye Z-H. 2012d. Three S, Lindner B, Puzo G, Gilleron M. 2011. Deciphering sulfoglycolipids Arabidopsis DUF579 domain-containing GXM proteins are methyl- of Mycobacterium tuberculosis. J Lipid Res 52:1098–1110. transferases catalyzing 4-O-methylation of glucuronic acid on xylan. Lazar IM, Lazar AC, Cortes DF, Kabulski JL. 2011. Recent advances in the Plant Cell Physiol 53:1934–1949. MS analysis of glycoproteins: Theoretical considerations. Electropho- Lee J, Lee J, Chung TD, Yeo W-S. 2012e. Nanoengineered micro gold shells resis 32:3–13. for LDI-TOF analysis of small molecules. Anal Chim Acta 736:1–6. Lazar L, Csavas M, Herczeg M, Herczegh P, Borbas A. 2012. Synthesis of S- Lee MH, Han JH, Kwon P-S, Bhuniya S, Kim JY, Sessler JL, Kang C, Kim linked glycoconjugates and S-disaccharides by thiol-ene coupling JS. 2012f. Hepatocyte-targeting single galactose-appended naphthali- reaction of enoses. Org Lett 14:4650–4653. mide: A tool for intracellular thiol imaging in vivo. J Am Chem Soc Lazar L, Janossy L, Csavas M, Herczeg M, Borbasa A, Antus S. 2012b. 134:1316–1322. Selective removal of the (2- naphthyl)methyl protecting group in the Lee YJ, Perdian DC, Song Z, Yeung ES, Nikolau BJ. 2012g. Use of mass presence of p-methoxybenzyl group by catalytic hydrogenation. spectrometry for imaging metabolites in plants. Plant J 70:81–95. Arkovic 312–325. Legrand F-X, Menand M, Sollogoub M, Tilloy S, Monflier E. 2011. An N- Lazar L, Mezo€ E, Herczeg M, Liptak A, Antus S, Borbas A. 2012c. Synthesis heterocyclic carbene ligand based on a b-cyclodextrin-imidazolium of the non-reducing end trisaccharide of the antithrombin-binding salt: Synthesis, characterization of organometallic complexes and domain of heparin and its bioisosteric sulfonic acid analogues. Suzuki coupling. New J Chem 35:2061–2065. Tetrahedron 68:7386–7399. Leon IR, Neves-Ferreira AGdC, da Rocha SLG, Trugilho MRdO, Perales J, Le TT, Deeth HC, Bhandari B, Alewood PF, Holland JW. 2012. A proteomic Valente RH. 2012. Using mass spectrometry to explore the neglected approach to detect lactosylation and other chemical changes in stored glycan moieties of the antiophidic proteins DM43 and DM64. milk protein concentrate. Food Chem 132:655–662. Proteomics 12:2753–2765. Leclere M, Kwok BK, Wu LK, Allan DS, Ben RN. 2011. C-Linked Levengood MR, Splain RA, Kiessling LL. 2011. Monitoring processivity antifreeze glycoprotein (C-AFGP) analogues as novel cryoprotectants. and length control of a carbohydrate polymerase. J Am Chem Soc Bioconjug Chem 22:1804–1810. 133:12758–12766.

Mass Spectrometry Reviews DOI 10.1002/mas 143 & HARVEY

Levy-Ontman O, Arad S, Harvey DJ, Parsons TB, Fairbanks A, Tekoah Y. Li Y, Mo H, Lian G, Yu B. 2012g. Revisit of the phenol O- glycosylation 2011. Unique N-glycan moieties of the 66-kDa cell wall glycoprotein with glycosyl imidates, BF3. OEt2 is a better catalyst than TMSOTf. from the red microalga Porphyridium sp. J Biol Chem 286:21340– Carbohydr Res 363:14–22. 21352. Li Y, Powell DA, Shaffer SA, Rasko DA, Pelletier MR, Leszyk JD, Scott AJ, Levy-Ontman O. 2012. N-Glycosylation of the 66-kDa cell-wall glycopro- Masoudi A, Goodlett DR, Wang X, Raetz CRH, Ernst RK. 2012h. LPS tein of a red microalga. In: Stefana P, editor. Glycosylation. Shanghai: remodeling is an evolved survival strategy for bacteria. Proc Natl Acad Intech. pp. 173–198. Chapter 8. Sci USA 109:8716–8721. Lewicky JD, Ulanova M, Jiang Z-H. 2011. Synthesis of a dimeric Liang L, Liu Z. 2011. A self-assembled molecular team of boronic acids at monosaccharide lipid A mimic and its synergistic effect on the the gold surface for specific capture of cis-diol biomolecules at neutral immunostimulatory activity of lipopolysaccharide. Carbohydr Res pH. Chem Commun 47:2255–2257. 346:1705–1713. Liang C-H, Wang S-K, Lin C-W, Wang C-C, Wong C-H, Wu C-Y. 2011a. Leymarie N, Zaia J. 2012. Effective use of mass spectrometry for Effects of neighboring glycans on antibody-carbohydrate interaction. glycan and glycopeptide structural analysis. Anal Chem 84:3040– Angew Chem Int Ed 50:1608–1612. 3048. Liang C-W, Lee C-H, Lee Y-T, Ni C-K. 2011b. Plume expansion dynamics Li B, Russell SC, Zhang J, Hedrick JL, Lebrilla CB. 2011a. Structure of matrix-assisted laser desorption ionization. Chem Asian J 6:2986– determination by MALDI- IRMPD mass spectrometry and exoglycosi- 2991. dase digestions of O-linked oligosaccharides from Xenopus borealis Liang YJ, Yang BC, Chen JM, Lin YH, Huang CL, Cheng YY, Hsu CY, egg jelly. Glycobiology 21:877–894. Khoo KH, Shen CN, Yu J. 2011c. Changes in glycosphingolipid Li H, Li N, Gao X, Kong X, Li S, Xu A, Jin S, Wu D. 2011b. High level composition during differentiation of human embryonic stem cells to expression of active recombinant human interleukin-3 in Pichia ectodermal or endodermal lineages. Stem Cell 29:1995–2004. pastoris. Protein Exp Purif 80:185–193. Liang C-W, Chang P-J, Lin Y-J, Lee Y-T, Ni C-K. 2012a. High ion yields of Li J, Li X, Guo Z, Yu L, Zou L, Liang X. 2011c. Click maltose as an carbohydrates from frozen solution by UV-MALDI. Anal Chem alternative to reverse phase material for desalting glycopeptides. 84:3493–3499. Analyst 136:4075–4082. Liang T-W, Hsieh J-L, Wang S-L. 2012b. Production and purification of a Li X, Zhou Z, Dai L, Zhou W, Wang J. 2011d. Synthesis and enantiosepara- protease, a chitosanase, and chitin oligosaccharides by Bacillus cereus tion characteristics of a novel mono-6-deoxy-(2,4-dihydroxybenzi- TKU022 fermentation. Carbohydr Res 362:38–46. mide)-b-cyclodextrin as a chiral stationary phase in high-performance Liao C-H, Yu J. 2012. Human embryonic stem cell differentiation: Role of liquid chromatography. Talanta 86:452–456. glycosphingolipid structure. In: Hayat MA, editor. Stem cells and Li X, Zhou Z, Zhou W, Dai L, Li Z. 2011e. Preparation of a novel cancer stem cells. Dordrecht: Springer ScienceþBusiness Media. pp. cyclodextrin derivative of benzimido-b-cyclodextrin and its enantiose- 179–190. paration performance in HPLC. Analyst 136:5017–5024. Liao J, Zhang R, Qian H, Cao L, Zhang Y, Xu W, Li J, Wu M, Yin Z. 2012. Li Y-T, Li S-C, Buck WR, Haskins ME, Wu S-W, Khoo K-H, Sidransky E, Serum profiling based on fucosylated glycoproteins for differentiating Bunnell BA. 2011f. Selective extraction and effective separation of between chronic hepatitis B and hepatocellular carcinoma. Biochem galactosylsphingosine (psychosine) and glucosylsphingosine from Biophys Res Commun 420:308–314. other glycosphingolipids in pathological tissue samples. Neurochem Liebminger E, Veit C, Pabst M, Batoux M, Zipfel C, Altmann F, Mach L, Res 36:1612–1622. Strasser R. 2011. b-N-Acetylhexosaminidases HEXO1 and HEXO3 Li Y, Sun J, Yu B. 2011g. Efficient synthesis of lupane-type saponins via are responsible for the formation of paucimannosidic N- glycans in gold(I)-catalyzed glycosylation with glycosyl ortho-alkynylbenzoates Arabidopsis thaliana. J Biol Chem 286:10793–10802. as donors. Org Lett 13:5508–5511. Lin Y-H, Tseng W-L. 2011. A sample preparation method for gold Li Y, Wang X, Ernst RK. 2011h. A rapid one-step method for the nanoparticle-assisted laser desorption/ionization time-of-flight mass characterization of membrane lipid remodeling in Francisella using spectrometry. Methods Mol Biol 790:167–172. matrix-assisted laser desorption ionization time-of-flight tandem mass Lin C-W, Chen J-M, Wang Y-M, Wu S-W, Tsai I-H, Khoo K-H. 2011a. spectrometry. Rapid Commun Mass Spectrom 25:2641–2648. Terminal disialylated multiantennary complex-type N-glycans carried Li Y, Sun J, Gong Y, Yu B. 2011i. Synthesis of oligomeric 4- (glycosyloxy) on acutobin define the glycosylation characteristics of the Deinagkis- benzoate macrocyclic glycosides. J Org Chem 76:3654–3663. trodon acutus venom. Glycobiology 21:530–542. Li H, Liu Z. 2012. Recent advances in monolithic column-based boronate- Lin W-L, Su W-W, Cai X-Y, Luo L-K, Li P-B, Wang Y-G. 2011b. affinity chromatography. Trends Anal Chem 37:148–161. Fermentation effects of oligosaccharides of Radix Ophiopogonis on alloxan-induced diabetes in mice. Int J Biol Macromol 49:194–200. Li B, Dobruchowska JM, Hoogenkamp MA, Gerwig GJ. 2012a. Structural investigation of an extracellular polysaccharide produced by the Lin Z-A, Zheng J-N, Lin F, Zhang L, Cai Z, Chen G-N. 2011c. Synthesis of cariogenic bacterium Streptococcus mutans strain UA159. Carbohydr magnetic nanoparticles with immobilized aminophenylboronic acid Polym 90:675–682. for selective capture of glycoproteins. J Mater Chem 21:518–524. Lin Z, Pang J, Yang H, Cai Z, Zhang L, Chen G. 2011d. One-pot synthesis of Li K, Xing R, Liu S, Li R, Qin Y, Meng X, Li P. 2012b. Separation of chito- an organic- inorganic hybrid affinity monolithic column for specific oligomers with several degrees of polymerization and study of their capture of glycoproteins. Chem Commun 47:9675–9677. antioxidant activity. Carbohydr Polym 88:896–903. Lin Z, Simeone DM, Anderson MA, Brand RE, Xie X, Shedden KA, Ruffin Li L, Ly M, Linhardt RJ. 2012c. Proteoglycan sequence. Mol Biosyst MT, Lubman DM. 2011e. Mass spectrometric assay for analysis 8:1613–1625. of haptoglobin fucosylation in pancreatic cancer. J Proteome Res Li P-B, Lin W-L, Wang Y-G, Peng W, Cai X-Y, Su W-W. 2012d. Antidiabetic 10:2602–2611. activities of oligosaccharides of Ophiopogonis japonicus in experimen- Lin ZA, Pang JL, Lin Y, Huang H, Cai ZW, Zhang L, Chen GN. 2011f. tal type 2 diabetic rats. Int J Biol Macromol 51:749–755. Preparation and evaluation of a phenylboronate affinity monolith for Li QK, Gabrielson E, Zhang H. 2012e. Application of glycoproteomics for selective capture of glycoproteins by capillary liquid chromatography. the discovery of biomarkers in lung cancer. Proteomics Clin Appl Analyst 136:3281–3288. 6:244–256. Lin C-Y, Ma Y-C, Pai P-J, Her G-R. 2012a. A comparative study of Li X, Wu P, Cheng S, Lv X. 2012f. Synthesis and assessment of globotriose- glycoprotein concentration, glycoform profile and glycosylation site chitosan conjugate, a novel inhibitor of shiga toxins produced by occupancy using isotope labeling and electrospray linear ion trap mass Escherichia coli. J Med Chem 55:2702–2710. spectrometry. Anal Chim Acta 728:49–56.

144 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Lin Y-C, Wang P-I, Kuo S-W. 2012b. Water-soluble, stable helical Liu JA, Xiong L, Zhang S, Wei JC, Xiong SX. 2012d. C60 Fluorine polypeptide-grafted cyclodextrin bioconjugates: Synthesis, secondary derivative as novel matrix for small molecule analysis by MALDI-TOF and self-assembly structures, and inclusion complex with guest MS. Metabolomics 2. Article 1000110. compounds. Soft Matter 8:9676–9684. Liu L, Bai Y, Sun N, Xia L, Lowary TL, Klassen JS. 2012e. Carbohydrate- Lin YH, Ghosh B, Mong K-KT. 2012c. In situ formation of b- glycosyl lipid interactions: Affinities of methylmannose polysaccharides for imidinium triflate from participating thioglycosyl donors: Elaboration lipids in aqueous solution. Chem Eur J 18:12059–12067. to disarmed-armed iterative glycosylation. Chem Commun 48:10910– Liu L, Zhang Y, Zhang L, Yan G, Yao J, Yang P, Lu H. 2012f. Highly specific 10912. revelation of rat serum glycopeptidome by boronic acid-functionalized Lin Z, Lo A, Simeone DM, Ruffin MT, Lubman DM. 2012d. An N- mesoporous silica. Anal Chim Acta 753:64–72. glycosylation analysis of human alpha-2-macroglobulin using an Liu R, Morales-Collazo O, Wei A. 2012g. Sulfoform generation from an integrated approach. J Proteomics Bioinform 5:127–134. orthogonally protected disaccharide. Carbohydr Res 355:19–27. Lindb€ack E, Zhou Y, Pedersen CM, Bols M. 2012. Two diastereomeric Liu T, Li X, Qian Y, Hu X, Liu S. 2012h. Multifunctional pH-disintegrable artificial enzymes with different catalytic activity. Eur J Org Chem micellar nanoparticles of asymmetrically functionalized b-cyclodex- 5366–5372. trin-based star copolymer covalently conjugated with doxorubicin and Ling NX-Y, Lee J, Ellis M, Liao M-L, Mau S-L, Guest D, Janssen PH, Kovac DOTA-Gd moieties. Biomaterials 33:2521–2531. P, Bacic A, Pettolino FA. 2012. An exo-b-(1-3)-D-galactanase from Liu Y, Lu Y, Liu Z. 2012i. Restricted access boronate affinity porous Streptomyces sp. provides insights into type II arabinogalactan monolith as a protein A mimetic for the specific capture of structure. Carbohydr Res 352:70–81. immunoglobulin G. Chem Sci 3:1467–1471. Lingg N, Zhang P, Song Z, Bardor M. 2012. The sweet tooth of Liu Y, Xia B, Gleason TJ, Castaneda~ U, He M, Berry GT, Fridovich-Keil JL. biopharmaceuticals: Importance of recombinant protein glycosylation 2012j. N- and O-linked glycosylation of total plasma glycoproteins in analysis. Biotechnol J 7:1462–1472. galactosemia. Mol Genet Metab 106:442–454. Linwei D, Peibo L, San LCB, Wa CY, Dingzhou X, Kwok-Pui F, Weiwei Liwanag AJM, Ebert B, Verhertbruggen Y, Rennie EA, Rautengarten C, S. 2012. Mechanistic studies on the antidiabetic activity of a Oikawa A, Andersen MCF, Clausen MH, Scheller HV. 2012. Pectin polysaccharide-rich extract of Radix ophiopogonis. Phytother Res biosynthesis: GALS1 in Arabidopsis thaliana is a b-1,4-galactan b- 26:101–105. 1,4-galactosyltransferase. Plant Cell 24:5024–5036. Lipinski T, Luu T, Kitov PI, Szpacenko A, Bundle DR. 2011. A structurally Lizak C, Fan Y-Y, Weber TC, Aebi M. 2011. N-Linked glycosylation of diversified linker enhances the immune response to a small carbohy- antibody fragments in Escherichia coli. Bioconjug Chem 22:488–496. drate hapten. Glycoconj J 28:149–164. Llobet E, Campos MA, Gimenez P, Moranta D, Bengoechea JA. 2011. Lira- Navarrete E, Valero- Gonzalez J, Villanueva R, Martnez-Julvez M, Analysis of the networks controlling the antimicrobial-peptide-depen- Tejero T, Merino P, Panjikar S, Hurtado-Guerrero R. 2011. Structural dent induction of Klebsiella pneumoniae virulence factors. Infect insights into the mechanism of protein O-fucosylation. PLoS One 6: Immun 79:3718–3732. e25365. Lo Conte M, Robb MJ, Hed Y, Marra A, Malkoch M, Hawker CJ, Dondoni Little DJ, Poloczek J, Whitney JC, Robinson H, Nitz M, Howell PL. 2012. A. 2011. Exhaustive glycosylation, PEGylation, and glutathionylation The structure- and metal-dependent activity of Escherichia coli PgaB of a [G4]-ene48 dendrimer via photoinduced thiol-ene coupling. J provides insight into the partial de-N-acetylation of poly-b-1,6-N- Polym Sci A 49:4468–4475. acetyl-D-glucosamine. J Biol Chem 287:31126–31137. Lo Conte M, Staderini S, Chambery A, Berthet N, Dumy P, Renaudet O, Liu C, Dong S, Xu X-J, Yin Y, Shriver Z, Capila I, Myette J, Venkataraman Marra A, Dondoni A. 2012. Glycoside and peptide clustering around G. 2011a. Assessment of the quality and structural integrity of a the octasilsesquioxane scaffold via photoinduced free-radical thiol-ene complex glycoprotein mixture following extraction from the formulat- coupling.The observation of a striking glycoside cluster effect. Org ed biopharmaceutical drug product. J Pharm Biomed Anal 54:27–36. Biomol Chem 10:3269–3277. Liu G, Han F, Yang Y, Xie Y, Jiang H, Mao Y, Wang H, Wang M, Chen R, Lobasso S, Lopalco P, Angelini R, Vitale R, Huber H, Muller€ V, Corcelli A. Yang J, Chen J. 2011b. Evaluation of sphingolipid metabolism in renal 2012. Coupled TLC and MALDI-TOF/MS analyses of the lipid extract cortex of rats with streptozotocin-induced diabetes and the effects of of the hyperthermophilic archaeon Pyrococcus furiosus. Archaea. rapamycin. Nephrol Dial Transplant 26:1493–1502. Article 957852. Liu Y-C, Yen H-Y, Chen C-Y, Chen C-H, Cheng P-F, Juan Y-H, Chen C-H, Locke LW, Mayo MW, Yoo AD, Williams MB, Berr SS. 2012. PET imaging 64 Khoo K-H, Yu C-J, Yang P-C, Hsu T-L, Wong C-H. 2011c. Sialylation of tumor associated macrophages using mannose coated Cu lip- and fucosylation of epidermal growth factor receptor suppress its osomes. Biomaterials 33:7785–7793. dimerization and activation in lung cancer cells. Proc Natl Acad Sci Lonardi E, Deelder AM, Wuhrer M, Balog CIA. 2012. Microarray USA 108:11332–11337. technology using glycans extracted from natural sources for serum Liu Y, Liu J, Yin P, Gao M, Deng C, Zhang X. 2011d. High throughput antibody fluorescent detection. Methods Mol Biol 808:285–302. identification of components from traditional Chinese medicine herbs Lopez M, Fort S, Bizot H, Buleon A, Driguez H. 2012. Chemo-enzymatic by utilizing graphene or graphene oxide as MALDI-TOF-MS matrix. J synthesis of xylogluco-oligosaccharides and their interactions with Mass Spectrom 46:804–815. cellulose. Carbohydr Polym 88:185–193. Liu R, Wei A. 2012. Solid-phase synthesis of 2-aminoethyl glucosamine Losfeld M-E, Leroy A, Coddeville B, Carpentier M, Mazurier J, Legrand D. sulfoforms. J Carbohydr Chem 31:384–419. 2011. N-glycosylation influences the structure and self-association Liu C-W, Chien M-W, Su C-Y, Chen H-Y, Li L-J, Lai C-C. 2012a. Analysis abilities of recombinant nucleolin. FEBS J 278:2552–2564. of flavonoids by graphene-based surface-assisted laser desorption/ Lourantos E, Ramirez OM, Giannakopulos AE, Beran KA, Derrick PJ, ionization time-of-flight mass spectrometry. Analyst 137:5809–5816. Bashir S. 2011. The use of a silica-based heat sink to uncouple the Liu J, Ru Q, Ding Y. 2012b. Glycation a promising method for food protein matrix-assisted laser desorption/ionization (MALDI) mechanism. modification: Physicochemical properties and structure, a review. Food Canad J Chem 89:446–460. Res Int 49:170–183. Loutet SA, Di Lorenzo F, Clarke C, Molinaro A, Valvano MA. 2011. Liu J, Cai Y-Z, Wong RNS, Lee CK-F, Tang SCW, Sze SCW, Tong Y, Transcriptional responses of Burkholderia cenocepacia to polymyxin Zhang Y. 2012c. Comparative analysis of caffeoylquinic acids and B in isogenic strains with diverse polymyxin B resistance phenotypes. lignans in roots and seeds among various burdock (Arctium lappa) BMC Genomics 12. Article 472. genotypes with high antioxidant activity. J Agric Food Chem 60:4067– Louvet R, Rayon C, Domon J-M, Rusterucci C, Fournet F, Leaustic A, 4075. Crepeau M-J, Ralet M-C, Rihouey C, Bardor M, Lerouge P, Gillet F,

Mass Spectrometry Reviews DOI 10.1002/mas 145 & HARVEY

Pelloux J. 2011. Major changes in the cell wall during silique Majer G, Csavas M, Lazar L, Herczeg M, Benyei A, Antus S, Borbas A. development in Arabidopsis thaliana. Phytochemistry 72:59–67. 2012. Synthesis of sulfonic acid-containing maltose-type keto-oligo- Lu I-C, Lin JL, Lai S-H, Chen C-H. 2011a. Frequency-scanning MALDI saccharides by an iterative approach. Tetrahedron 68:4986–4994. linear ion trap mass spectrometer for large biomolecular ion detection. Makaravicius T, Basinskiene L, Juodeikiene G, van Gool MP, Schols HA. Anal Chem 83:8273–8277. 2012. Production of oligosaccharides from extruded wheat and rye Lu M, Lai Y, Chen G, Cai Z. 2011b. Matrix interference-free method biomass using enzymatic treatment. Catalysis Today 196:16–25. for the analysis of small molecules by using negative ion laser Maki T. 2012. Quantitative approach for small molecules using laser desorption/ionization on graphene flakes. Anal Chem 83:3161– desorption/ionization mass spectrometry. Biol Pharm Bull 35:1413– 3169. 1416. Lu Z, Madico G, Roche MI, Wang Q, Hui JH, Perkins HM, Zaia J, Costello Makszin L, Kilar A, FelsoP,P eterfi Z, Kocsis B, Kilar F. 2012. Quantitative CE, Sharon J. 2012. Protective B-cell epitopes of Francisella tularensis microfluidic analysis of S- and R-type endotoxin components with chip O-polysaccharide in a mouse model of respiratory tularaemia. Immu- capillary electrophoresis. Electrophoresis 33:3351–3360. nol Cell Biol 136:352–360. Mallard I, Landy D, Bouchemal N, Fourmentin S. 2011. Synthesis and Lucas R, Gmez-Pinto I, Avi A, Reina JJ, Eritja R, Gonzlez C, Morales JC. inclusion ability of anthracene appended b-cyclodextrins: Unexpected 2011. Highly polar carbohydrates stack onto DNA duplexes via CH/p effect of triazole linker. Carbohydr Res 346:35–42. interactions. J Am Chem Soc 133:1909–1916. Mamedov T, Yusibov V. 2011. Green algae Chlamydomonas reinhardtii Luczkowiak J, Sattin S, Sutkeviciute ˙ I, Reina JJ, Sanchez-Navarro M, possess endogenous sialylated N-glycans. FEBS Open Biol 1:15–22. Thepaut M, Martnez-Prats L, Daghetti A, Fieschi F, Delgado R, Mandal SM. 2012. A novel hydroxyproline rich glycopeptide from pericarp Bernardi A, Rojo J. 2011. Pseudosaccharide functionalized dendrimers of Datura stramonium: Proficiently eradicate the biofilm of antifungals as potent inhibitors of DC-SIGN dependent Ebola pseudotyped viral resistant Candida albicans. Peptide Sci 98:332–337. infection. Bioconjug Chem 22:1354–1365. Mangiapia G, Coppola C, Vitiello G, D’Errico G, De Napoli L, Radulescu A, Lumholdt LR, Holm R, Jørgensen EB, Larsen KL. 2012. In vitro Montesarchio D, Paduano L. 2011. Nanostructuring of CyPLOS investigations of a-amylase mediated hydrolysis of cyclodextrins in (Cyclic Phosphate-Linked oligoSaccharides), novel saccharide-based the presence of ibuprofen, flurbiprofen, or benzo[a] pyrene. Carbohydr synthetic ion transporters. J Colloid Interf Sci 354:718–724. Res 362:56–61. Luo L-Z, Jin H-W, Huang H-Q. 2011. Application of capillary isoelectric Manju S, Sreenivasan K. 2011. Conjugation of curcumin onto hyaluronic focusing and peptide mass fingerprinting in carbohydrate-deficient acid enhances its aqueous solubility and stability. J Colloid Interf Sci transferrin detection. Rapid Commun Mass Spectrom 25:1391–1398. 359:318–325. Lutteke€ T. 2012. The use of glycoinformatics in glycochemistry. Beilstein J Mann BF, Goetz JA, House MG, Schmidt CM, Novotny MV. 2012. Org Chem 8:915–929. Glycomic and proteomic profiling of pancreatic cyst fluids identifies hyperfucosylated lactosamines on the N-linked glycans of overex- Lv X, Yu S, Wang J, Du Y. 2011. Synthesis of stryphnoside A, a triterpene pressed glycoproteins. Mol Cell Proteomics 11:M111.015792. saponin isolated from the pericarps of Stryphnodendron fissuratum. Carbohydr Res 346:1786–1791. Marcobal A, Barboza M, Sonnenburg ED, Pudlo N, Martens EC, Desai P, Lebrilla CB, Weimer BC, Mills DA, German JB, Sonnenburg JL. 2011. Ma Q, Sun S, Meng X-B, Li Q, Li S-C, Li Z-J. 2011a. Assembly of Bacteroides in the infant gut consume milk oligosaccharides via homolinear a(1- 2)-linked nonamannoside on ionic liquid support. J mucus-utilization pathways. Cell Host Microbe 10:507–514. Org Chem 76:5652–5660. Mari A, Napolitano A, Perrone A, Pizza C, Piacente S. 2012. An analytical Ma Y, Li Z, Shi H, Zhang J, Yu B. 2011b. Assembly of digitoxin by gold(I)- approach to profile steroidal saponins in food supplements: The case of catalyzed glycosidation of glycosyl o-alkynylbenzoates. J Org Chem Ruscus aculeatus. Food Chem 134:461–468. 76:9748–9756. € Ma Z, Bertolo L, Arar S, Monteiro MA. 2011c. TEMPO-mediated Marsching C, Eckhardt M, Grone H-J, Sandhoff R, Hopf C. 2011. Imaging glycoconjugation: A scheme for the controlled synthesis of polysac- of complex sulfatides SM3 and SB1a in mouse kidney using MALDI- charide conjugates. Carbohydr Res 346:343–347. TOF/TOF mass spectrometry. Anal Bioanal Chem 401:53–64. Ma W-F, Li L-L, Zhang Y, An Q, You L-J, Li J-M, Zhang Y-T, Xu S, Yu M, Marsh JT, Tryfona T, Powers SJ, Stephens E, Dupree P, Shewry PR, Guo J, Lu H-J, Wang C-C. 2012. Ligand-free strategy for ultrafast and Lovegrove A. 2011. Determination of the N- glycosylation patterns of highly selective enrichment of glycopeptides using Ag-coated magnet- seed proteins: Applications to determine the authenticity and substan- ic nanoarchitectures. J Mater Chem 22:23981–23988. tial equivalence of genetically modified (GM) crops. J Agric Food Chem 59:8779–8788. Machado E, Kandzia S, Carilho R, Altevogt P, Conradt HS, Costa J. 2011. N- Glycosylation of total cellular glycoproteins from the human ovarian Martinez EA, Boer H, Koivula A, Samain E, Driguez H, Armand S, Cottaz S. carcinoma SKOV3 cell line and of recombinantly expressed human 2012. Engineering chitinases for the synthesis of chitin oligosacchar- erythropoietin. Glycobiology 21:376–386. ides: Catalytic amino acid mutations convert the GH-18 family Madala NE, Leone MR, Molinaro A, Dubery IA. 2011. Deciphering the glycoside hydrolases into transglycosylases. J Mol Catal B Enzymatic structural and biological properties of the lipid A moiety of lip- 74:89–96. opolysaccharides from Burkholderia cepacia strain ASP B 2D, in Martirosyan A, Perez-Gutierrez C, Banchereau R, Dutartre H, Lecine P, Arabidopsis thaliana. Glycobiology 21:184–194. Dullaers M, Mello M, Salcedo SP, Muller A, Leserman L, Levy Y, Maeda K, Mochizuki H, Osato K, Yashima E. 2011. Stimuli-responsive Zurawski G, Zurawski S, Moreno E, Moriyon I, Klechevsky E, helical poly (phenylacetylene)s bearing cyclodextrin pendants that Banchereau J, Oh S, Gorvel J-P. 2012. Brucella b-1,2-cyclic glucan is exhibit enantioselective gelation in response to chirality of a chiral an activator of human and mouse dendritic cells. PLoS Pathog 8: amine and hierarchical super-structured helix formation. Macromole- e1002983. cules 44:3217–3226. Martos-Maldonado MC, Quesada-Soriano I, Casas-Solvas JM, Garca- Maeda E, Kita S, Kinoshita M, Urakami K, Hayakawa T, Kakehi K. 2012. Fuentes L, Vargas-Berenguel A. 2012. Secondary face-to-face 2-2’ b- Analysis of nonhuman N-glycans as the minor constituents in recombi- cyclodextrin dimers linked with fluorescent rigid spacer arms: A nant monoclonal antibody pharmaceuticals. Anal Chem 84:2373– cyclodextrin-based ratiometric sensor for bile salts. Eur J Org Chem 2379. 2560–2571. Mainente F, Simonato B, Zoccatelli G, Rizzi C. 2011. A method for the Massen ZS, Sarli VC, Coutouli-Argyropoulou E, Gallos JK. 2011. Synthesis preparative separation of beer proteins and glycocompounds. J Inst of C- glycosylated amino acids by hetero-Diels-Alder addition of ethyl Brewing 117:435–439. 2-nitrosoacrylate to exo- glycals. Carbohydr Res 346:230–237.

146 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Maszczak-Seneczko D, Olczak T, Jakimowicz P, Olczak M. 2011. Over- Mechref Y, Hu Y, Garcia A, Hussein A. 2012. Identifying cancer biomarkers expression of UDP-GlcNAc transporter partially corrects galactosyla- by mass spectrometry-based glycomics. Electrophoresis 33:1755– tion defect caused by UDP-Gal transporter mutation. FEBS Lett 1767. 585:3090–3094. Mechref Y, Hu Y, Garcia A, Zhou S, Desantos-Garcia JL, Hussein A. 2012. Matsui K, Nazifi E, Kunita S, Wada N, Matsugo S, Sakamoto T. 2011. Novel Defining putative glycan cancer biomarkers by MS. Bioanalysis glycosylated mycosporine-like amino acids with radical scavenging 4:2457–2469. activity from the cyanobacterium Nostoc commune. J Photochem Medina SH, Tekumalla V, Chevliakov MV, Shewach DS, Ensminger WD, Photobiol B 105:81–89. El-Sayed MEH. 2011. N-Acetylgalactosamine-functionalized den- Matsuno Y-K, Dong W, Yokoyama S, Yonezawa S, Saito T, Gotoh M, drimers as hepatic cancer cell-targeted carriers. Biomaterials 32:4118– Narimatsu H, Kameyama A. 2011. Improved method for immuno- 4129. staining of mucin separated by supported molecular matrix electropho- Meevissen MHJ, Balog CIA, Koeleman CAM, Doenhoff MJ, Schramm G, resis by optimizing the matrix composition and fixation procedure. Haas H, Deelder AM, Wuhrer M. 2011. Targeted glycoproteomic Electrophoresis 32:1829–1836. analysis reveals that kappa-5 is a major, uniquely glycosylated Matsuo K. 2011. Small-scale, high-throughput method for plant N-glycan component of Schistosoma mansoni egg antigens. Mol Cell Proteomics preparation for matrix-assisted laser desorption/ionization time-of- 10:M119.005710. flight mass spectrometry analysis. Anal Biochem 413:200–202. Meevissen MHJ, Driessen NN, Smits HH, Versteegh R, van Vliet SJ, van Matsuo K, Matsumura T. 2011. Deletion of fucose residues in plant N- Kooyk Y, Schramm G, Deelder AM, Haas H, Yazdanbakhsh M, Hokke glycans by repression of the GDP-mannose 4,6-dehydratase gene using CH. 2012. Specific glycan elements determine differential binding of virus-induced gene silencing and RNA interference. Plant Biotechnol J individual egg glycoproteins of the human parasite Schistosoma 9:264–281. mansoni by host C-type lectin receptors. Int J Parasitol 42:269–277. Matsuoka K, Yamaguchi H, Kohzu T, Sakamoto J-I, Koyama T, Hatano K, Mehdy A, Morelle W, Rosnoblet C, Legrand D, Lefebvre T, Duvet S, Yamamoto S, Mori T, Hatanaka K. 2012. Convenient assembly of Foulquier F. 2012. PUGNAc treatment leads to an unusual accumula- trimeric Lex determinants using carbosilane scaffolds by means of tion of free oligosaccharides in CHO cells. J Biochem (Tokyo) Huisgen cycloaddition. Tetrahedron Lett 53:6793–6796. 151:439–446. Matsuura M, Kawasaki K, Kawahara K, Mitsuyama M. 2012. Evasion of Meiland M, Liebert T, Baumgaertel A, Schubert US, Heinze T. 2011. Alkyl human innate immunity without antagonizing TLR4 by mutant b-D-cellulosides: non-reducing cellulose mimics. Cellulose 18:1585– Salmonella enterica serovar Typhimurium having penta-acylated lipid 1598. A. Innate Immun 18:764–773. Meinke S, Schroven A, Thiem J. 2011. Sialic acid C-glycosides with Matwiejuk M, Thiem J. 2011. New method for regioselective glycosylation aromatic residues: Investigating enzyme binding and inhibition of employing saccharide oxyanions. Eur J Org Chem 5860–5878. Trypanosoma cruzi trans- sialidase. Org Biomol Chem 9:4487–4497. Matwiejuk M, Thiem J. 2012. Hydroxy group acidities of partially protected Meisen I, Mormann M, Muthing€ J. 2011. Thin-layer chromatography, glycopyranosides. Eur J Org Chem 2180–2187. overlay technique and mass spectrometry: A versatile triad advancing Mavlonov GT, Lee JM, Shin H-S, Yi T-H, Abdurakhmonov IY. 2011. Low glycosphingolipidomics. Biochim Biophys Acta 1811:875–896. molecular fucoidan and its macromolecular complex with bee venom Meixner M, Jungnickel J, Grothe C, Gieselmann V, Eckhardt M. 2011. melittin. Adv Biosci Biotechnol 2:298–303. Myelination in the absence of UDP-galactose: Ceramide galactosyl- May JF, Levengood MR, Splain RA, Brown CD, Kiessling LL. 2012. A transferase and fatty acid 2-hydroxylase. BMC Neurosci 12: Article processive carbohydrate polymerase that mediates bifunctional cataly- 22. sis using a single active site. Biochemistry 51:1148–1159. Mengbar M, Ganan M, Miralles B, Carrascosa AV, Martnez-Rodriguez AJ, Mayampurath AM, Wu Y, Segu ZM, Mechref Y, Tang H. 2011. Improving Peter MG, Heras A. 2011. Antibacterial activity of products of confidence in detection and characterization of protein N-glycosylation depolymerization of chitosans with lysozyme and chitosanase against sites and microheterogeneity. Rapid Commun Mass Spectrom Campylobacter jejuni. Carbohydr Polym 84:844–848. 25:2007–2019. Mergy J, Fournier A, Hachet E, Auzely-Velty R. 2012. Modification of Mazanec K, Dycka F, Bobalova J. 2011. Monitoring of barley starch polysaccharides via thiol-ene chemistry: A versatile route to functional amylolysis by gravitational field flow fractionation and MALDI-TOF biomaterials. J Polym Sci A 50:4019–4028. MS. J Sci Food Agric 91:2756–2761. Merrill AHJ. 2011. Sphingolipid and glycosphingolipid metabolic pathways Mazola Y, Chinea G, Musacchio A. 2011. Integrating bioinformatics tools to in the era of sphingolipidomics. Chem Rev 111:6387–6422. handle glycosylation. PLoS Comp Biol 7:e1002285. Miao Y, Rousseau C, Mortreux A, Martin P, Zinck P. 2011. Access to new Mazumder K, Pena~ MJ, O’Neill MA, York WS. 2012. Structural characteri- carbohydrate-functionalized polylactides via organocatalyzed ring- zation of the heteroxylans from poplar and switchgrass. Methods Mol opening polymerization. Polymer 52:5018–5026. Biol 908:215–228. Michel-Cuello C, Ortiz-Cerda I, Moreno-Vilet L, Grajales-Lagunes A, Mazurek J, Ignatowicz L, Kallenius G, Svenson SB, Pawlowski A, Hamasur Moscosa-Santillan M, Bonnin J, Gonzalez-Chavez MM, Ruiz-Cabrera B. 2012. Divergent effects of mycobacterial cell wall glycolipids on M. 2012. Study of enzymatic hydrolysis of fructans from Agave maturation and function of human monocyte-derived dendritic cells. salmiana: Characterization and kinetic assessment. Sci World J. Article PLoS One 7:e42515. 863432. Mazzaferro LS, Pinuel~ L, Erra-Balsells R, Giudicessi SL, Breccia JD. 2012. Miedes E, Zarra I, Hoson T, Herbers K, Sonnewald U, Lorences EP. 2011. Transglycosylation specificity of Acremonium sp. a-rhamnosyl-b- Xyloglucan endotransglucosylase and cell wall extensibility. J Plant glucosidase and its application to the synthesis of the new fluorogenic Physiol 168:196–203. substrate 4-methylumbelliferyl-rutinoside. Carbohydr Res 347:69–75. Milhomme O, Kohler€ SM, Ropartz D, Lesur D, Pilard S, Djeda€ni-Pilard F, McCormick SP, Price NPJ, Kurtzman CP. 2012. Glucosylation and other Beyer W, Grandjean C. 2012. Synthesis and immunochemical evalua- biotransformations of T-2 toxin by yeasts of the Trichomonascus clade. tion of a non-methylated disaccharide analogue of the anthrax Appl Environ Microbiol 78:8694–8702. tetrasaccharide. Org Biomol Chem 10:8524–8532. Meany DL, Chan DW. 2011. Aberrant glycosylation associated with Mille C, Fradin C, Delplace F, Trinel P-A, Masset A, FrancoisS N, Coddeville enzymes as cancer biomarkers. Clin Proteomics 8. Article 7. B, Bobrowicz P, Jouault T, Guerardel Y, Wildt S, Janbon G, Poulain D. Mechref Y. 2011. Analysis of glycans derived from glycoconjugates by 2012. Members 5 and 6 of the Candida albicans BMT family encode capillary electrophoresis-mass spectrometry. Electrophoresis 32:3467– enzymes acting specifically on b-mannosylation of the phospholipo- 3481. mannan cell-wall glycosphingolipid. Glycobiology 22:1332–1342.

Mass Spectrometry Reviews DOI 10.1002/mas 147 & HARVEY

Miller AK, Brannon MK, Stevens L, Johansen HK, Selgrade SE, Miller SI, Moldt B, Shibata-Koyama M, Rakasz EG, Schultz N, Kanda Y, Dunlop DC, Høiby N, Moskowitz SM. 2011. PhoQ mutations promote lipid A Finstad SL, Jin C, Landucci G, Alpert MD, Dugast A-S, Parren PWHI, modification and polymyxin resistance of Pseudomonas aeruginosa Nimmerjahn F, Evans DT, Alter G, Forthal DN, Schmitz JE, Iida S, found in colistin- treated cystic fibrosis patients. Antimicrob Agents Poignard P, Watkins DI, Hessell AJ, Burtona DR. 2012. A non- Chemother 55:5761–5769. fucosylated variant of the anti-HIV-1 monoclonal antibody b12 has Millon MBB, Delgado MA, Azar NB, Guelbert N, Sturiale L, Garozzo D, enhanced FcgRIIIa-mediated antiviral activity in vitro but does not Matthijs G, Jaeken J, de Kremer RD, Asteggiano CG. 2011. Two improve protection against mucosal SHIV challenge in macaques. J Argentinean siblings with CDG-Ix: A novel type of congenital disorder Virol 86:6189–6196. of glycosylation? JIMD Rep 1:65–72. Møllegaard KM, Duus K, Træholt SD, Thaysen-Andersen M, Liu Y, Palma Minig M, Mazzaferro LS, Erra-Balsells R, Petroselli G, Breccia JD. 2011. a- AS, Feizi T, Hansen PR, Højrup P, Houen G. 2011. The interactions of Rhamnosyl-b-glucosidase-catalyzed reactions for analysis and bio- calreticulin with immunoglobulin G and immunoglobulin Y. Biochim transformations of plant-based foods. J Agric Food Chem 59:11238– Biophys Acta 1814:889–899. 11243. Mong K-KT, Yen Y-F, Hung W-C, Lai Y-H, Chen J-H. 2012. Application of Misaki R, Sakai Y, Omasa T, Fujiyama K, Seki T. 2011. N-terminal vacuolar 2-azido-2-deoxythioglycosides for b-glycoside formation and oligo- sorting signal at the mouse antibody alters the N-linked glycosylation saccharide synthesis. Eur J Org Chem 3009–3017. pattern in suspension-cultured tobacco BY2 cells. J Biosci Bioeng Monteiro MA, Britton S, Applebee LA, Baqar S. 2011. Synthesis and 112:476–484. immunogenicity of a Helicobacter pylori lipopolysaccharide-based Mischnick P. 2012. Mass spectrometric characterization of oligo- and conjugate. Vaccine 29:3098–3102. polysaccharides and their derivatives. Adv Polym Sci 248:105–174. Montesino R, Calvo L, Vallin A, Rudd PM, Harvey DJ, Cremata JA. 2012. N Mishra A, Kavita K, Jha B. 2011a. Characterization of extracellular Structural characterization of -linked oligosaccharides on monoclonal antibody Nimotuzumab through process development. Biologicals polymeric substances produced by micro-algae Dunaliella salina. Carbohydr Polym 83:852–857. 40:288–298. Montilla A, Olano A, Martnez-Villaluenga C, Corzo N. 2011. Study of Mishra AK, Krumbach K, Rittmann D, Appelmelk B, Pathak V, Pathak AK, influential factors on oligosaccharide formation by fructosyltransferase Nigou J, Geurtsen J, Eggeling L, Besra GS. 2011b. Lipoarabinomannan activity during stachyose hydrolysis by Pectinex Ultra SP-L. J Agric biosynthesis in Corynebacterineae: The interplay of two a(1,2)- Food Chem 59:10705–10711. mannopyranosyltransferases MptC and MptD in mannan branching. Mol Microbiol 80:1241–1259. Morava E, Lefeber DJ, Wevers RA. 2011. Protein glycosylation and congenital disorders of glycosylation. Protein Rev 13:97–117. Mishra AK, Alves JE, Krumbach K, Nigou J, Castro AG, Geurtsen J, ~ Eggeling L, Saraiva M, Besra GS. 2012a. Differential arabinan capping Moreira ASP, Coimbra MA, Nunes FM, Simoes J, Domingues MRM. 2011. of lipoarabinomannan modulates innate immune responses and im- Evaluation of the effect of roasting on the structure of coffee pacts T helper cell differentiation. J Biol Chem 287:44173–44183. galactomannans using model oligosaccharides. J Agric Food Chem 59:10078–10087. Mishra AK, Krumbach K, Rittmann D, Batt SM, Lee OY-C, De S, Frunzke J, Besra GS, Eggeling L. 2012b. Deletion of manCinCorynebacterium Mori T, Kodera T, Yoshimine H, Kakuta Y, Sugiura N, Kimata K, Okahata glutamicum results in a phospho-myo-inositol mannoside- and lip- Y. 2012. Kinetics of iterative carbohydrate transfer to polysaccharide oglycan-deficient mutant. Microbiology 158:1908–1917. catalyzed by chondroitin polymerase on a highly sensitive flow- type 27MHz quartz-crystal microbalance. Chem Eur J 18:7388– Mitsui Y, Yamada K, Hara S, Kinoshita M, Hayakawa T, Kakehi K. 7393. 2012. Comparative studies on glycoproteins expressing polylactosamine-type N-glycans in cancer cells. J Pharm Biomed Anal 70:718– Morisue M, Ueda S, Kurasawa M, Naito M, Kuroda Y. 2012. Highly 726. fluorescent slipped-cofacial phthalocyanine dimer as a shallow inclusion complex with a-cyclodextrin. J Phys Chem A 116:5139–5144. Miura Y, Onogi S, Fukuda T. 2012. Syntheses of sulfo-glycodendrimers using click chemistry and their biological evaluation. Molecules Morita T, Ishibashi Y, Fukuoka T, Imura T, Sakai H, Abe M, Kitamoto D. 17:11877–11896. 2011a. Production of glycolipid biosurfactants, cellobiose lipids, by Cryptococcus humicola JCM 1461 and their interfacial properties. Miyata S, Yamakawa N, Toriyama M, Sato C, Kitajima K. 2011. Co- Biosci Biotechnol Biochem 75:1597–1599. expression of two distinct polysialic acids, a2,8- and a2,9-linked polymers of N-acetylneuraminic acid, in distinct glycoproteins and Morita T, Ishibashi Y, Hirose N, Wada K, Takahashi M, Fukuoka T, Imura T, glycolipids in sea urchin sperm. Glycobiology 21:1596–1605. Sakai H, Abe M, Kitamoto D. 2011b. Production and characterization of a glycolipid biosurfactant, mannosylerythritol lipid B, from sugar- Mkhikian H, Grigorian A, Li CF, Chen H-L, Newton B, Zhou RW, Beeton C, cane juice by Ustilago scitaminea NBRC 32730. Biosci Biotechnol Torossian S, Tatarian GG, Lee S-U, Lau K, Walker E, Siminovitch KA, Biochem 75:1371–1376. Chandy KG, Yu Z, Dennis JW, Demetriou M. 2011. Genetics and the Morita T, Fukuoka T, Imura T, Kitamoto D. 2012. Formation of the two environment converge to dysregulate N-glycosylation in multiple novel glycolipid biosurfactants, mannosylribitol lipid and mannosylar- sclerosis. Nat Commun 2:334–346. abitol lipid, by Pseudozyma parantarctica JCM 11752T. Appl Micro- Mo K-F, Fang T, Stalnaker SH, Kirby PS, Liu M, Wells L, Pierce M, Live biol Biotechnol 96:931–938. DH, Boons G-J. 2011. Synthetic, structural, and biosynthetic studies of Motteram J, Lovegrove A, Pirie E, Marsh J, Devonshire J, van de Meene A, an unusual phospho-glycopeptide derived from a-dystroglycan. J Am Hammond-Kosack K, Rudd JJ. 2011. Aberrant protein N-glycosylation Chem Soc 133:14418–14430. impacts upon infection-related growth transitions of the haploid plant- Mo K-F, Li X, Li H, Low LY, Quinn CP, Boons G-J. 2012. Endolysins of pathogenic fungus Mycosphaerella graminicola. Mol Microbiol Bacillus anthracis bacteriophages recognize unique carbohydrate 81:415–433. epitopes of vegetative cell wall polysaccharides with high affinity and Moty an JA, Fazekas E, Mori H, Svensson B, Bagossi P, Kandra L, Gyemant selectivity. J Am Chem Soc 134:15556–15562. G. 2011. Transglycosylation by barley a-amylase 1. J Mol Catal B Mohiman N, Argentini M, Batt SM, Cornu D, Masi M, Eggeling L, Besra G, Enzymatic 72:229–237. Bayan N. 2012. The ppm operon is essential for acylation and Mounfield WPI, Garrett TJ. 2012. Automated MALDI matrix coating system glycosylation of lipoproteins in Corynebacterium glutamicum. PLoS for multiple tissue samples for imaging mass spectrometry. J Am Soc One 7:e46225. Mass Spectrom 23:563–569. Moker€ J, Thiem J. 2012. Synthesis and hydrolysis studies of novel glyco- Mourya VK, Inamdar NN, Choudhari YM. 2011. Chitooligosaccharides: functionalized platinum complexes. Carbohydr Res 348:14–26. Synthesis, characterization and applications. Polym Sci A 53:583–612.

148 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Mrazek H, Benada O, Mand P, Vanek O, Kren V, Bezouska K, Weignerova Nagels B, Van Damme EJM, Pabst M, Callewaert N, Weterings K. 2011. L. 2012. Facile production of Aspergillus niger a-N-acetylgalactosa- Production of complex multiantennary N-glycans in Nicotiana ben- minidase in yeast. Protein Exp Purif 81:106–114. thamiana plants. Plant Physiol 155:1103–1112. Mugunthan G, Sriram D, Yogeeswari P, Kartha KPR. 2011a. Synthesis Nagels B, Van Damme EJM, Callewaert N, Weterings K. 2012. Introduction and biological evaluation of sugar-derived chiral nitroimidazoles of tri-antennary N-glycans in Arabidopsis thaliana plants. Plant Sci as potential antimycobacterial agents. Carbohydr Res 346:1760– 185–186:161–168. 1766. Nagorny P, Sane N, Fasching B, Aussedat B, Danishefsky SJ. 2012. Probing Mugunthan G, Ramakrishna K, Sriram D, Yogeeswari P, Kartha KPR. the frontiers of glycoprotein synthesis: The fully elaborated b-subunit 2011b. Synthesis and screening of galactose-linked nitroimidazoles of the human follicle-stimulating hormone. Angew Chem Int Ed and triazoles against Mycobacterium tuberculosis. Eur J Med Chem 51:975–979. 46:4725–4732. Nagy M, Racz D, Daroczi L, Lukacs B, Jona I, Zsuga M, Keki S. 2011. Mugunthan G, Sriram D, Yogeeswari P, Kartha KPR. 2012. Synthesis and Synthesis and characterization of an amphiphilic blue-light-emitting preliminary screening of O-b-D-galactopyranosides as potential mimic glycosylated poly (naphthalene/phenylene) copolymer. Macromol of UDP-Galp against Mycobacterium tuberculosis. J Carbohydr Chem Chem Phys 212:1891–1899. 31:553–570. Naka T, Maeda S, Niki M, Ohara N, Yamamoto S, Yano I, Maeyama J-i Mugunthan G, Ramakrishna K, Sriram D, Yogeeswari P, Kartha KPR. Ogura H, Kobayashi K, Fujiwara N. 2011a. Lipid phenotype of two 2011c. Synthesis and screening of (E)-1- (b-D-galactopyranosyl)-4- distinct subpopulations of Mycobacterium bovis Bacillus Calmette- (aryl)but-3-ene-2-one against Mycobacterium tuberculosis. Bioorg Guerin Tokyo 172 substrain. J Biol Chem 286:44153–44161. Med Chem Lett 21:3947–3950. Naka T, Nakata N, Maeda S, Yamamoto R, Doe M, Mizuno S, Niki M, Muller€ C, Wagner K, Frankenfeld K, Franzreb M. 2011. Simplified Kobayashi K, Ogura H, Makino M, Fujiwara N. 2011b. Structure and purification of equine chorionic gonadotropin (eCG)—An example of host recognition of serotype 13 glycopeptidolipid from Mycobacterium the use of magnetic microsorbents for the isolation of glycoproteins intracellulare. J Bacteriol 193:5766–5774. from serum. Biotechnol Lett 33:929–936. Nakagawa A, Kamitakahara H, Takano T. 2011a. Synthesis of blockwise Muller€ A, Ulm H, Reder-Christ K, Sahl H-G, Schneider T. 2012a. Interaction alkylated (1-4) linked trisaccharides as surfactants: Influence of of type A lantibiotics with undecaprenol-bound cell envelope precur- configuration of anomeric position on their surface activities. Carbo- sors. Microb Drug Resist 18:261–270. hydr Res 346:1671–1683. Muller€ A, Munch€ D, Schmidt Y, Reder-Christ K, Schiffer G, Bendas G, Nakagawa A, Fenn D, Koschella A, Heinze T, Kamitakahara H. 2011b. Gross H, Sahl H-G, Schneider T, Brotz-Oesterhelt€ H. 2012b. Lip- Synthesis of diblock methylcellulose derivatives with regioselective odepsipeptide empedopeptin inhibits cell wall biosynthesis through functionalization patterns. J Polym Sci A 49:4964–4976. 2þ Ca -dependent complex formation with peptidoglycan precursors. J Nakagawa M, Tojo H, Fuji S. 2011c. A glycan of C-factor from Biol Chem 287:20270–20280. Dictyostelium discoideum contains a bisecting-GlcNAc, an intersect- Mun J-Y, Lee KJ, Kim YJ, Kwon O, Kim S-J, Lee S-G, Park WS, Heo WD, ing-GlcNAc, and a core a-1,6-fucose. Biosci Biotechnol Biochem Oh D-B. 2012. Development of fluorescent probes for the detection of 75:1964–1970. fucosylated N-glycans using an Aspergillus oryzae lectin. Appl Micro- Nakagawa T, Nishi Y, Kondo A, Shirai Y, Honda C, Asahi M, Tanimoto T. biol Biotechnol 93:251–260. 2011d. Preparation, characterization, and biological evaluation of I IV Munoz-Garc~ a JC, Lopez-Prados J, Angulo J, Daz-Contreras I, Reichardt N, 6 ,6 -di-O-[a-L- fucopyranosyl-(1-6)-2-acetamido-2-deoxy-b-D-glu- de Paz JL, Martn-Lomas M, Nieto PM. 2012. Effect of the substituents copyranosyl]-cyclomaltoheptaose and 6-O-[a-L-fucopyranosyl-(1-6)- of the neighboring ring in the conformational equilibrium of iduronate 2-acetamido-2-deoxy- b-D-glucopyranosyl]-cyclomaltoheptaose. Car- in heparin-like trisaccharides. Chem Eur J 18:16319–16331. bohydr Res 346:1792–1800. Musapelo T, Murray KK. 2011. Particle formation in ambient MALDI Nakagawa A, Kamitakahara H, Takano T. 2012. Synthesis and thermorever- plumes. Anal Chem 83:6601–6608. sible gelation of diblock methylcellulose analogues via Huisgen 1,3- Muszynski A, Laus M, Kijne JW, Carlson RW. 2011. Structures of dipolar cycloaddition. Cellulose 19:1315–1326. the lipopolysaccharides from Rhizobium leguminosarum RBL5523 and Nakamura I, Makino A, Horikawa Y, Sugiyama J, Ohmae M, Kimura S. its UDP-glucose dehydrogenase mutant (exo5). Glycobiology 21:55– 2011a. Preparation of fibrous cellulose by enzymatic polymerization 68. using cross-linked mutant endoglucanase II. Chem Commun Muzashvili T, Perrone A, Napolitano A, Kemertelidze E, Pizza C, Piacente 47:10127–10129. S. 2011. Caucasicosides E-M, furostanol glycosides from Helleborus Nakamura T, Nishikaze T, Jinmei H, Tougasaki F, Sugimoto I, Amano J. caucasicus. Phytochem Lett 72:2180–2188. 2011b. Quantitative matrix-assisted laser desorption/ionization mass Naberezhnykh GA, Gorbach VI, Bratskaya SY, Soloveva TF. 2011. spectrometry of pyrene-derivatized glycopeptides for investigation of Preparation and properties of liposomes coated with N-acylated low- mammalian cell glycomics. J Glycom Lipidom 1: Article 1000103. molecular-weight chitosan. Chem Nat Compds 46:852–856. Nangia S, Garrison BJ. 2011. Molecular dynamics simulations of matrix Nacev BA, Grassi P, Dell A, Haslam SM, Liu JO. 2011. The antifungal drug assisted laser desorption ionization: Matrix-analyte interactions. Nucl itraconazole inhibits vascular endothelial growth factor receptor 2 Instrum Meth B 269:1744–1747. (VEGFR2) glycosylation, trafficking, and signaling in endothelial Napolitano A, Muzashvili T, Perrone A, Pizza C, Kemertelidze E, Piacente cells. J Biol Chem 286:44045–44056. S. 2011. Steroidal glycosides from Ruscus ponticus. Phytochemistry Nagai K-I, Takahashi N, Moue T, Niimura Y. 2011. Alteration of fatty 72:651–661. acid molecular species in ceramide and glucosylceramide under heat Naresh K, Bharati BK, Avaji PG, Chatterji D, Jayaraman N. 2011. Synthesis, stress and expression of sphingolipid-related genes. Adv Biol Chem biological studies of linear and branched arabinofuranoside-containing 1:35–48. glycolipids and their interaction with surfactant protein A. Glycobiol- Nagel L, Plattner C, Budke C, Majer Z, DeVries AL, Berkemeier T, Koop T, ogy 21:1237–1254. Sewald N. 2011. Synthesis and characterization of natural and modified Naresh K, Avaji PG, Maiti K, Bharati BK, Syal K, Chatterji D, Jayaraman N. antifreeze glycopeptides: Glycosylated foldamers. Amino Acids 2012. Synthesis of b-arabinofuranoside glycolipids, studies of their 41:719–732. binding to surfactant protein-A and effect on sliding motilities of M. Nagel L, Budke C, Erdmann RS, Dreyer A, Wennemers H, Koop T, Sewald smegmatis. Glycoconj J 29:107–118. N. 2012. Influence of sequential modifications and carbohydrate Natsuka S, Hirohata Y, Nakakita S-i Sumiyoshi W, Hase S. 2011. Structural variations in synthetic AFGP analogues on conformation and anti- analysis of N-glycans of the planarian Dugesia japonica. FEBS J freeze activity. Chem Eur J 18:12783–12793. 278:452–460.

Mass Spectrometry Reviews DOI 10.1002/mas 149 & HARVEY

Natsuka S. 2012. One-step purification method for pyridylamino glycans. Nishimura S-I. 2011. Toward automated glycan analysis. Adv Carbohydr Biosci Biotechnol Biochem 76:1982–1983. Chem Biochem 65:219–271. Natunen S, Satomaa T, Pitk€anen V, Salo H, Mikkola M, Natunen J, Nishimura S-I. 2012. Development of fully automated glycan analytical Otonkoski T, Valmu L. 2011. The binding specificity of the marker system. Jpn J Clin Chem 41:257–258. antibodies Tra-1-60 and Tra-1-81 reveals a novel pluripotency- Nishimura S-I, Hato M, Hyugaji S, Feng F, Amano M. 2012. Glycomics for associated type 1 lactosamine epitope. Glycobiology 21:1125–1130. drug discovery: Metabolic perturbation in androgen-independent Naumann I, Klein BC, Bartel SJ, Darsow KH, Buchholz R, Lange HA. 2011. prostate cancer cells induced by unnatural hexosamine mimics. Angew Identification of sulfoquinovosyldiacyglycerides from Phaeodactylum Chem Int Ed 51:3386–3390. tricornutum by matrix-assisted laser desorption/ionization QTrap time- Nishiyama K-i, Maeda M, Yanagisawa K, Nagase R, Komura H, Iwashita T, of-flight hybrid mass spectrometry. Rapid Commun Mass Spectrom Yamagaki T, Kusumoto S, Tokuda H, Shimamoto K. 2012. MPIase is a 25:2517–2523. glycolipozyme essential for membrane protein integration. Nat Com- Nayak B, Berrios JDJ, Powers JR, Tang J. 2011. Thermal degradation of mun 3: Article 1260. anthocyanins from purple potato (Cv. Purple Majesty) and impact on Niwa Y, Suzuki T, Dohmae N, Umezawa K, Simizu S. 2012. Determination antioxidant capacity. J Agric Food Chem 59:11040–11049. of cathepsin V activity and intracellular trafficking by N-glycosylation. Nazarenko EL, Crawford RJ, Ivanova EP. 2011. The structural diversity of FEBS Lett 586:3601–3607. carbohydrate antigens of selected gram-negative marine bacteria. Mar Noble GT, Craven FL, Voglmeir J, Sardz k R, Flitsch SL, Webb SJ. 2012. Drugs 9:1914–1954. Accelerated enzymatic galactosylation of N-acetylglucosaminolipids Negishi K, Mashiko Y, Yamashita E, Otsuka A, Hasegawa T. 2011. Cellulose in lipid microdomains. J Am Chem Soc 134:13010–13017. chemistry meets click chemistry: Syntheses and properties of cellu- Noguchi M, Fujieda T, Huang WC, Ishihara M, Kobayashi A, Shoda S-I. lose-based glycoclusters with high structural homogeneity. Polym Adv 2012. A practical one-step synthesis of 1,2-oxazoline derivatives from Technol 3:489–508. unprotected sugars and its application to chemoenzymatic b-N- Nepogodiev SA, Fais M, Hughes DL, Field RA. 2011. Synthesis of apiose- acetylglucosaminidation of disialo-oligosaccharide. Helvetica Chi- containing oligosaccharide fragments of the plant cell wall: Fragments mica Acta 95:1928–1936. of rhamnogalacturonan-II side chains A and B, and apiogalacturonan. Noh SM, Han SE, Shim G, Lee KE, Kim C-W, Han SS, Choi Y, Kim YK, Org Biomol Chem 9:6670–6684. Kim W-K, Oh Y-K. 2011. Tocopheryl oligochitosan-based self Nett JH, Stadheim TA, Li H, Bobrowicz P, Hamilton SR, Davidson RC, Choi assembling oligomersomes for siRNA delivery. Biomaterials 32:849– B-K, Mitchell T, Bobrowicz B, Rittenhour A, Wildt S, Gerngross TU. 857. 2011. A combinatorial genetic library approach to target heterologous Nohara T, Imamura A, Yamaguchi M, Hidari KIPJ, Suzuki T, Komori T, glycosylation enzymes to the endoplasmic reticulum or the Golgi Ando H, Ishida H, Kiso M. 2012. Design and synthesis of a apparatus of Pichia pastoris. Yeast 28:237–252. novel ganglioside ligand for influenza A viruses. Molecules 17:9590– Nett JH, Gomathinayagam S, Hamilton SR, Gong B, Davidson RC, Du M, 9620. Hopkins D, Mitchell T, Mallem MR, Nylen A, Shaikh SS, Sharkey N, Nokami T, Nozaki Y, Saigusa Y, Shibuya A, Manabe S, Ito Y, Yoshida J-I. Barnard GC, Copeland V, Liu L, Evers R, Li Y, Gray PM, Lingham 2011. Glycosyl sulfonium ions as storable intermediates for glycosyla- RB, Visco D, Forrest G, DeMartino J, Linden T, Potgieter TI, Wildt S, tions. Org Lett 13:1544–1547. Stadheim TA, d’Anjou M, Li H, Sethuraman N. 2012. Optimization of Nonami H, Gholipour Y, Erra-Balsells R. 2011. Direct tissue and cell erythropoietin production with controlled glycosylation-PEGylated analysis of tulip bulbs by combining pressure probe and UV-MALDI- erythropoietin produced in glycoengineered Pichia pastoris. J Bio- MS. Acta Horticult 923:53–58. technol 157:198–206. Norberg AL, Dybvik AI, Zakariassen H, Mormann M, Peter-KatalinicJ, Nhiem NX, Lim HY, Kiem PV, Minh CV, Thu VK, Tai BH, Quang TH, Song Eijsink VGH, Sørlie M. 2011. Substrate positioning in chitinase A, a SB, Kim YH. 2011. Oleanane-type triterpene saponins from the bark of processive chito-biohydrolase from Serratia marcescens. FEBS Lett Aralia elata and their NF-jB inhibition and PPAR activation signal 585:2339–2344. pathway. Bioorg Med Chem Lett 21:6143–6147. Normand M, Kirillov E, Carpentier J-F, Guillaume SM. 2012. Cyclodextrin- Nichols FC, Bajrami B, Clark RB, Housley W, Yao X. 2012. Free lipid A centered polyesters: Controlled ring-opening polymerization of cyclic isolated from Porphyromonas gingivalis lipopolysaccharide is contam- esters from b-cyclodextrin-diol. Macromolecules 45:1122–1130. inated with phosphorylated dihydroceramide lipids: Recovery in North SJ, von Gunten S, Antonopoulos A, Trollope A, MacGlashan DWJ, diseased dental samples. Infect Immun 80:860–874. Jang-Lee J, Dell A, Metcalfe DD, Kirshenbaum AS, Bochner BS, Nie H, Li Y, Sun X-L. 2012. Recent advances in sialic acid-focused Haslam SM. 2012. Glycomic analysis of human mast cells, eosinophils glycomics. J Proteomics 75:3098–3112. and basophils. Glycobiology 22:12–22. Nimptsch K, Suß€ R, Schnabelrauch M, Nimptsch A, Schiller J. 2012. Novakova V, Kobak RZU, Kucera R, Kopecky K, Miletin M, KrepsovaV, Positive ion MALDI-TOF mass spectra are more suitable than negative Ivincovac J, Zimcikc P. 2012. The effect of the number of carbohydrate ion spectra to characterize sulphated glycosaminoglycan oligosacchar- moieties on the azaphthalocyanine properties. Dalton Trans 41:10596– ides. Int J Mass Spectrom 310:72–76. 10604. Nishikaze T, Nakamura T, Jinmei H, Amano J. 2011. Negative-ion MALDI- Novikov OO, Pisarev DI, Zhilyakova ET, Novikova MU, Bondarenko EV, MS2 for discrimination of a2,3- and a2,6-sialylation on glycopeptides Fadeeva DA, Bezmenova MD. 2011. Phytochemical study of the labeled with a pyrene derivative. J Chromatogr B 879:1419–1428. North Caucasian Rosa spinossima L. fruit. Bull Exp Biol Med Nishikaze T, Okumura H, Jinmei H, Amano J. 2012a. Correlation between 152:216–218. sweet spots of glycopeptides and polymorphism of the matrix crystal in Novoa-Carballal R, Muller€ AHE. 2012. Synthesis of polysaccharide-b-PEG MALDI samples. Mass Spectrom 1: Article A0006. block copolymers by oxime click. Chem Commun 48:3781–3783. Nishikaze T, Kaneshiro K, Kawabata S-I, Tanaka K. 2012b. Structural Nuevo-Ordonez~ Y, Montes-Bayon M, Gonzolez EB, Sanz-Medel A. 2011. analysis of N-glycans by the glycan-labeling method using 3-amino- Titanium preferential binding sites in human serum transferrin at quinoline-based liquid matrix in negative-ion MALDIMS. Anal Chem physiological concentrations. Metallomics 3:1297–1303. 84:9453–9461. Nycholat CM, McBride R, Ekiert DC, Xu R, Rangarajan J, Peng W, Razi N, Nishikaze T, Fukuyama Y, Kawabata S-I, Tanaka K. 2012c. Sensitive Gilbert M, Wakarchuk W, Wilson IA, Paulson JC. 2012. Recognition analyses of neutral N-glycans using anion-doped liquid matrix G3CA of sialylated poly-N-acetyllactosamine chains on N- and O-linked by negative-ion matrix-assisted laser desorption/ionization mass spec- glycans by human and avian influenza A virus hemagglutinins. Angew trometry. Anal Chem 84:6097–6103. Chem Int Ed 51:4860–4863.

150 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Nystrom€ K, Le Gall-Recule G, Grassi P, Abrantes J, Ruvoe¨n-Clouet N, Le self-assembled monolayer-coated quantum dots. J Am Chem Soc Moullac-Vaidye B, Lopes AM, Esteves PJ, Strive T, Marchandeau S, 133:12507–12517. Dell A, Haslam SM, Le Pendu J. 2011. Histo-blood group antigens act Oikawa A, Saito K. 2012. Metabolite analyses of single cells. Plant J 70:30– as attachment factors of rabbit hemorrhagic disease virus infection in a 38. virus strain-dependent manner. PLoS One 7:e1002188. Oka H, Koyama T, Hatano K, Matsuoka K. 2012. Synthetic studies of bi- Nyuchev AV, Sharonova EA, Lenshina NA, Shavyrin AS, Lopatin MA, fluorescence-labeled maltooligosaccharides as substrates for a-amy- Balalaeva IV, Beletskaya IP, Fedorov AY. 2011. Synthesis of fluores- lase on the basis of fluorescence resonance energy transfer (FRET). cent coumarin triazolylglycosides. Tetrahedron Lett 52:4196–4199. Bioorg Med Chem 20:435–445. O’Mahony AM, Ogier J, Desgranges S, Cryan JF, Darcy R, O’Driscoll CM. Okada H, Fukushi E, Yamamori A, Kawazoe N, Onodera S, Kawabata J, 2012. A click chemistry route to 2-functionalised PEGylated and Shiomi N. 2011. Isolation and structural confirmation of the oligosac- cationic b-cyclodextrins: co-formulation opportunities for siRNA charides containing a-D-fructofuranoside linkages isolated from fer- delivery. Org Biomol Chem 10:4954–4960. mented beverage of plant extracts. Carbohydr Res 346:2633–2637. Oberli MA, Hecht M-L, Bindsch€adler P, Adibekian A, Adam T, Seeberger Oliveira LMA, Lages A, Gomes RA, Neves H, Familia C, Coelho AV, PH. 2011. A possible oligosaccharide-conjugate vaccine candidate Quintas A. 2011. Insulin glycation by methylglyoxal results in native- for Clostridium difficile is antigenic and immunogenic. Chem Biol like aggregation and inhibition of fibril formation. BMC Biochem 12: 18:580–588. Article 41. Obermajer N, Sattin S, Colombo C, Bruno M. 2011. Design, synthesis and Oliver CM. 2011. Insight into the glycation of milk proteins: An ESI- and activity evaluation of mannose-based DC-SIGN antagonists. Mol MALDI-MS perspective. Crit Rev Food Sci Nutr 51:410–431. Divers 15:347–360. Olrichs NK, Aarsman MEG, Verheul J, Arnusch CJ, Martin NI, HerveM, Oefner CM, Winkler A, Hess C, Lorenz AK, Holecska V, Huxdorf M, Vollmer W, de Kruijff B, Breukink E, den Blaauwen T. 2011. A novel Schommartz T, Petzold D, Bitterling J, Schoen A-L, Stoehr AD, Van in vivo cell-wall labeling approach sheds new light on peptidoglycan DV, Darcan-Nikolaisen Y, Blanchard V, Schmudde I, Laumonnier Y, synthesis in Escherichia coli. ChemBioChem 12:1124–1133. Strover€ HA, Hegazy AN, Eiglmeier S, Schoen CT, Mertes MMM, Oman TJ, Boettcher JM, Wang H, Okalibe XN, van der Donk WA. 2011. Loddenkemper C, Lohning€ M, Konig€ P, Petersen A, Luger EO, Collin Sublancin is not a lantibiotic but an S-linked glycopeptide. Nat Chem M, Kohl€ J, Hutloff A, Hamelmann E, Berger M, Wardemann H, Ehlers Biol 7:78–80. M. 2012. Tolerance induction with T cell-dependent protein antigens Ongay S, Boichenko A, Govorukhina N, Bischoff R. 2012. Glycopeptide induces regulatory sialylated IgGs. J Allergy Clin Immunol 129:1647– enrichment and separation for protein glycosylation analysis. J Sep Sci 1655. 35:2341–2372. Offengenden M, Fentabil MA, Wu J. 2011. N-glycosylation of ovomucin Onitsuka M, Kim W-D, Ozaki H, Kawaguchi A, Honda K, Kajiura H, from hen egg white. Glycoconj J 28:113–123. Fujiyama K, Asano R, Kumagai I, Ohtake H, Omasa T. 2012. Ogata M, Yano M, Umemura S, Murata T, Park EY, Kobayashi Y, Asai T, Enhancement of sialylation on humanized IgG-like bispecific antibody Oku N, Nakamura N, Matsuo I, Usui T. 2012. Design and synthesis of by overexpression of a2,6-sialyltransferase derived from Chinese high-avidity tetravalent glycoclusters as probes for Sambucus sieboldi- hamster ovary cells. Appl Microbiol Biotechnol 94:69–80. ana agglutinin and characterization of their binding properties. Onoue K, Zaima N, Sugiura Y, Isojima T, Okayama S, Horii M, Akai Y, Bioconjug Chem 23:97–105. Uemura S, Takemura G, Sakuraba H, Sakaguchi Y, Setou M, Saito Y. Ogawa S, Ito M, Ohki H, Kimura T, Shimizu T, Matsuda M, Miyairi K. 2011. Using imaging mass spectrometry to accurately diagnose Fabry’s 2012a. Glycosylation status and conformational stability of recombi- disease. Circulation J 75:221–223. nant Stereum purpureum endopolygalacturonase IVs produced in an Oppenheimer SR, Drexler DM. 2012. Tissue analysis by imaging MS. Aspergillus oryzae expression system. J Appl Glycosci 59:37–42. Bioanalysis 4:95–112. Ogawa Y, Yoshiyama C, Kitaoka T. 2012b. Helical assembly of azobenzene- Otani M, Nakata J, Kihara M, Leroy V, Moll S, Wada Y, Izui S. 2012a. O- conjugated carbohydrate hydrogelators with specific affinity for Glycosylated IgA rheumatoid factor induces IgA deposits and glomer- lectins. Langmuir 28:4404–4412. ulonephritis. J Am Soc Nephrol 23:438–446. Ogorek C, Jordan I, Sandig V, von Horsten HH. 2012. Fucose-targeted Otani M, Kuroki A, Kikuchi S, Kihara M, Nakata J, Ito K, Furukawa J-I, glycoengineering of pharmaceutical cell lines. Methods Mol Biol Shinohara Y, Izui S. 2012b. Sialylation determines the nephritogenicity 907:507–517. of IgG3 cryoglobulins. J Am Soc Nephrol 23:1869–1878. Ohkawabata S, Kanemaru M, Kuawahara S-Y, Yamamoto K, Kadokawa J-I. Otto NJ, Solakyildirim K, Linhardt RJ, DeAngelis PL. 2011. Comamonas 2012. Synthesis of 6-O-hexadecyl- and 6-O-octylsucroses and their testosteronan synthase, a bifunctional glycosyltransferase that produ- self-assembling properties under aqueous conditions. J Carbohydr ces a unique heparosan polysaccharide analog. Glycobiology 21:1331– Chem 31:659–672. 1340. Ohmae M, Kurosaki K, Makino A, Kobayashi S. 2011. Enzymatic Otto NJ, Green DE, Masuko S, Mayer A, Tanner ME, Linhardt RJ, polymerization to an alternating N-phthaloyl chitin derivative cata- DeAngelis PL. 2012. Structure/function analysis of Pasteurella lyzed by chitinase. Chem Lett 40:194–195. multocida heparosan synthases: Toward defining enzyme specificity Ohnuma T, Numata T, Osawa T, Mizuhara M, Va˚rum KM, Fukamizo T. and engineering novel catalysts. J Biol Chem 287:7203–7212. 2011a. Crystal structure and mode of action of a class V chitinase from Overath T, Kuckelkorn U, Henklein P, Strehl B, Bonar D. 2012. Mapping of Nicotiana tabacum. Plant Mol Biol 75:291–304. O-GlcNAc sites of 20S proteasome subunits and Hsp90 by a novel Ohnuma T, Numata T, Osawa T, Mizuhara M, Lampela O, Juffer AH, Skriver biotin-cystamine tag. Mol Cell Proteomics 11:467–477. K, Fukamizo T. 2011b. A class V chitinase from Arabidopsis thaliana: Oya-Ito T, Naito Y, Takagi T, Handa O, Matsui H, Yamada M, Shima K, Gene responses, enzymatic properties, and crystallographic analysis. Yoshikawa T. 2011. Heat-shock protein 27 (Hsp27) as a target of Planta Med 234:123–137. methylglyoxal in gastrointestinal cancer. Biochim Biophys Acta Ohnuma T, Fukuda T, Dozen S, Honda Y, Kitaoka M, Fukamizo T. 2012. A 1812:769–781. glycosynthase derived from an inverting GH19 chitinase from the moss Ozawa K, Wakasa Y, Ogo Y, Matsuo K, Kawahigashi H, Takaiwa F. 2012. Bryum coronatum. Biochem J 444:437–443. Development of an efficient agrobacterium-mediated gene targeting Ohyanagi T, Nagahori N, Shimawaki K, Hinou H, Yamashita T, Sasaki A, Jin system for rice and analysis of rice knockouts lacking granule-bound T, Iwanaga T, Kinjo M, Nishimura S-I. 2011. Importance of sialic acid starch synthase (waxy) and b1,2- xylosyltransferase. Plant Cell Physiol residues illuminated by live animal imaging using phosphorylcholine 53:755–761.

Mass Spectrometry Reviews DOI 10.1002/mas 151 & HARVEY

Ozohanics O, Turiak L, Drahos L, Vekey K. 2012. Comparison of glycans in human fungal pathogen Cryptococcus neoformans by glycopeptide/glycoprotein enrichment techniques. Rapid Commun glycomics analysis. J Biol Chem 287:19501–19515. Mass Spectrom 26:215–217. Park JH, Wang Z, Jeong H-J, Park HH, Kim B-G, Tan W-S, Choi SS, Park Ozug J, Wudyka S, Gunay NS, Beccati D, Lansing J, Wang J, Capila I, TH. 2012d. Enhancement of recombinant human EPO production and Shriver Z, Kaundinya GV. 2012. Structural elucidation of the glycosylation in serum-free suspension culture of CHO cells through tetrasaccharide pool in enoxaparin sodium. Anal Bioanal Chem expression and supplementation of 30Kc19. Appl Microbiol Biotech- 403:2733–2744. nol 96:671–683. Pabst M, Altmann F. 2011. Glycan analysis by modern instrumental Parsons CL, Proctor J, Teichman JS, Nickel JC, Davis E, Evans R, Zupkas P, methods. Proteomics 11:631–643. Phillips C, Shaw T, Naidu N, Argade S. 2011. A multi-site study Pacharra S, Hanisch F-G, Breloy I. 2012. Neurofascin 186 is O-mannosy- confirms abnormal glycosylation in the Tamm-Horsfall protein of lated within and outside of the mucin domain. J Proteome Res patients with interstitial cystitis. J Urol 186:112–116. 11:3955–3964. Parsons J, Altmann F, Arrenberg CK, Koprivova A, Beike AK, Stemmer C, Palma AS, Zhang Y, Childs RA, Campanero-Rhodes MA, Ten Feizi YL, Gorr G, Reski R, Decker EL. 2012. Moss-based production of asialo- Chai W. 2012. Neoglycolipid-based designer oligosaccharide micro- erythropoietin devoid of Lewis A and other plant-typical carbohydrate arrays to define b-glucan ligands for dectin-1. Methods Mol Biol determinants. Plant Biotechnol J 10:851–861. 808:337–359. Paschinger K, Razzazi-Fazeli E, Furukawa K, Wilson IBH. 2011. Presence Palmberger D, Rendic D, Tauber P, Krammer F, Wilson IBH, Grabherr R. of galactosylated core fucose on N-glycans in the planaria Dugesia 2011. Insect cells for antibody production: Evaluation of an efficient japonica. J Mass Spectrom 46:561–567. alternative. J Biotechnol 153:160–166. Paschinger K, Gonzalez-Sapienza GG, Wilson IBH. 2012a. Mass spectro- Palmberger D, Wilson IBH, Berger I, Grabherr R, Rendic D. 2012. metric analysis of the immunodominant glycan epitope of Echinococ- SweetBac: A new approach for the production of mammalianised cus granulosus antigen Ag5. Int J Parasitol 42:279–285. glycoproteins in insect cells. PLoS One 7:e34226. Paschinger K, Hykollari A, Razzazi-Fazeli E, Greenwell P, Leitsch D, Palmisano G, Lendal SE, Larsen MR. 2011. Titanium dioxide enrichment of Walochnik J, Wilson IBH. 2012b. The N-glycans of Trichomonas sialic acid-containing glycopeptides. Methods Mol Biol 753:309–322. vaginalis contain variable core and antennal modifications. Glycobiol- Palmisano G, Melo-Braga MN, Engholm-Keller K, Parker BL, Larsen MR. ogy 22:300–313. 2012. Chemical deamidation: A common pitfall in large-scale N-linked Pasek M, Ramakrishnan B, Boeggeman E, Mercer N, Dulcey AE, Griffiths glycoproteomic mass spectrometry-based analyses. J Proteome Res GL, Qasba PK. 2012. The N-acetyl-binding pocket of N-acetylglucosa- 11:1949–1957. minyltransferases also accommodates a sugar analog with a chemical Pampati PK, Suravajjala S, Dain JA. 2011. Monitoring nonenzymatic handle at C2. Glycobiology 33:379–388. glycation of human immunoglobulin G by methylglyoxal and glyoxal: Pathigoolla A, Gonnade RG, Sureshan KM. 2012. Topochemical click A spectroscopic study. Anal Biochem 408:59–63. reaction: Spontaneous self-stitching of a monosaccharide to linear Pan S, Chen R, Aebersold R, Brentnall TA. 2011a. Mass spectrometry based oligomers through lattice-controlled azide-alkyne cycloaddition. An- glycoproteomics-from a proteomics perspective. Mol Cell Proteomics gew Chem Int Ed 51:4362–4366. 10:M110.002731. Pati D, Shaikh AY, Hotha S, Gupta SS. 2011. Synthesis of glycopolypeptides O a N Pan X, Sengupta P, Webster DC. 2011b. Novel biobased epoxy compounds: by the ring opening polymerization of -glycosylated- -amino acid - carboxyanhydride (NCA). Polym Chem 2:805–811. Epoxidized sucrose esters of fatty acids. Green Chem 13:965–975. Panchadhayee R, Misra AK. 2011. Convergent synthesis of the pentasac- Pati D, Kalva N, Das S, Kumaraswamy G, Gupta SS, Ambade AV. 2012a. charide repeating unit of the O-antigen of Shigella boydii type 14. Multiple topologies from glycopolypeptide-dendron conjugate self- assembly: Nanorods, micelles, and organogels. J Am Chem Soc 134: Tetrahedron Asym 22:1390–1394. 7796–7802. Pang P-C, Chiu PCN, Lee C-L, Chang L-Y, Panico M, Morris HR, Haslam SM, Khoo K-H, Clark GF, Yeung WSB, Dell A. 2011. Human sperm Pati D, Shaikh AY, Das S, Nareddy PK, Swamy MJ, Hotha S, Sen Gupta S. x O binding is mediated by the sialyl-Lewis oligosaccharide on the zona 2012b. Controlled synthesis of -glycopolypeptide polymers and their pellucida. Science 333:1761–1764. molecular recognition by lectins. Biomacromolecules 13:1287–1295. Patil RS, Ahire KM, Ramana CV. 2012. Stereospecific synthesis of C- Paper JM, Scott-Craig JS, Cavalier D, Faik A, Wiemels RE, Borrusch MS, Bongers M, Walton JD. 2012. a-Fucosidases with different substrate arabinofuranosides and carba-disaccharide analogues of Motif C of specificities from two species of Fusarium. Appl Microbiol Biotechnol cell wall AG complex of Mtb. Tetrahedron Lett 53:6347–6350. 97:5371–5380. Pawlaczyk I, Czerchawski L, Kuliczkowski W, Karolko B, Pilecki W, Park J-N, Song Y, Cheon SA, Kwon O, Oh D-B, Jigami Y, Kim J-Y, Kang Witkiewicz W, Gancarz R. 2011. Anticoagulant and anti-platelet activity of polyphenolic-polysaccharide preparation isolated from the HA. 2011a. Essential role of YlMPO1, a novel Yarrowia lipolytica Erigeron canadensis homologue of Saccharomyces cerevisiae MNN4, in mannosylphos- medicinal plant L. Thromb Res 127:328–340. phorylation of N- and O-linked glycans. Appl Environ Microbiol Pazynina GV, Popova IS, Belyanchikov IM, Tuzikov AB, Bovin NV. 2012. c 77:1187–1195. Synthesis of trisaccharide 6’SiaLe and its 6-O-Su derivative. Mende- Park JK, Chung MJ, Choi HN, Park YI. 2011b. Effects of the molecular leev Commun 22:194–195. weight and the degree of deacetylation of chitosan oligosaccharides on Pedersen JW, Bennett EP, Schjoldager KT-BG, Meldal M, Holmer AP, Blixt antitumor activity. Int J Mol Sci 12:266–277. O, Clo E, Levery SB, Clausen H, Wandall HH. 2011a. Lectin domains Park YB, Cosgrove DJ. 2012. Changes in cell wall biomechanical properties of polypeptide GalNAc transferases exhibit glycopeptide binding in the xyloglucan-deficient xxt1/xxt2 mutant of Arabidopsis. Plant specificity. J Biol Chem 286:32684–32696. Physiol 158:465–475. Pedersen JW, Blixt O, Bennett EP, Tarp MA, Dar I, Mandel U, Poulsen SS, Park E, Yang H, Kim Y, Kim J. 2012a. Analysis of oligosaccharides in beer Pedersen AE, Rasmussen S, Jess P, Clausen H, Wandall HH. 2011b. using MALDI-TOF-MS. Food Chem 134:1658–1664. Seromic profiling of colorectal cancer patients with novel glycopeptide Park G-H, Baek JM, Le HT, Lim CW, Kim TW. 2012. Cooperative microarray. Int J Cancer 128:1860–1871. perfunctionalization and partial labeling of 6-azido-6-deoxy-a-cyclo- Pedersen CM, Figueroa-Perez I, Ulmer AJ, Z€aahringer U, Schmidt RR. dextrin through copper(I)-catalyzed azide-alkyne cycloaddition. Tetra- 2012a. Synthesis of the repeating unit of the lipoteichoic acid of hedron Lett 53:5911–5915. Streptococcus pneumoniae. Tetrahedron 68:1052–1061. Park J-N, Lee D-J, Kwon O, Oh D-B, Bahn Y-S, Kang HA. 2012c. Pedersen HL, Fangel JU, McCleary B, Ruzanski C, Rydahl MG, Ralet M-C, Unraveling unique structure and biosynthesis pathway of N-linked Farkas V, von Schantz L, Marcus SE, Andersen MCF, Field R, Ohlin

152 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

M, Knox JP, Clausen MH, Willats WGT. 2012b. Versatile high Pichert A, Samsonov SA, Theisgen S, Thomas L, Baumann L, Schiller J, resolution oligosaccharide microarrays for plant glycobiology and cell Beck-Sickinger AG, Huster D, Pisabarro MT. 2012. Characterization wall research. J Biol Chem 287:39429–39438. of the interaction of interleukin-8 with hyaluronan, chondroitin sulfate, Pellikaan WF, Stringano E, Leenaars J, Bongers DJGM, Schuppen SvL-v, dermatan sulfate and their sulfated derivatives by spectroscopy and Plant J, Mueller-Harvey I. 2011. Evaluating effects of tannins on extent molecular modeling. Glycobiology 22:134–145. and rate of in vitro gas and CH4 production using an automated Pilolli R, Palmisano F, Cioffi N. 2012. Gold nanomaterials as a new tool for pressure evaluation system (APES). Animal Feed Sci Technol 166– bioanalytical applications of laser desorption ionization mass spec- 167:377–390. trometry. Anal Bioanal Chem 402:601–623. Peltier J, Courtin P, El Meouche I, Lemee L, Chapot-Chartier M-P, Pons J-L. Pinero~ T, Peres VJ, Katzin A, Couto AS. 2012. Metabolic oligosaccharide 2011. Clostridium difficile has an original peptidoglycan structure with engineering of Plasmodium falciparum intraerythrocytic stages allows a high level of N-acetylglucosamine deacetylation and mainly 3-3 direct glycolipid analysis by mass spectrometry. Mol Biochem Para- cross-links. J Biol Chem 286:29053–29062. sitol 182:88–92. Pena~ MJ, Kong Y, York WS, O’Neill MA. 2012. A galacturonic acid- Pinto G, Caira S, Cuollo M, Fierro O, Nicolai MA, Chianese L, Addeo F. containing xyloglucan is involved in Arabidopsis root hair tip growth. 2012. Lactosylated casein phosphopeptides as specific indicators of Plant Cell 24:4511–4524. heated milks. Anal Bioanal Chem 402:1961–1972. Pena~ MJ, Tuomivaara ST, Urbanowicz BR, O’Neill MA, York WS. 2012. Pirkl A, Soltwisch J, Draude F, Dreisewerd K. 2012. Infrared matrix-assisted Methods for structural characterization of the products of cellulose- laser desorption/ionization orthogonal-time-of-flight mass spectrome- and xyloglucan-hydrolyzing enzymes. Methods Enzymol 510:121– try employing a cooling stage and water ice as a matrix. Anal Chem 139. 84:5669–5676. Peng W, Jayasuriya AB, Imamura A, Lowary TL. 2011. Synthesis of the 6- Plattner C, Hfener M, Sewald N. 2011. One-pot azidochlorination of glycals. O-methyl-D-glycero-a-L-gluco-heptopyranose moiety present in the Org Lett 13:545–547. capsular polysaccharide from Campylobacter jejuni NCTC 11168. Org Plesner B, Westh P, Hvidt S, Nielsen AD. 2011. The molar hydrodynamic Lett 13:5290–5293. volume changes of factor VIIa due to GlycoPEGylation. J Pharm Peng F, Peng P, Xu F, Sun R-C. 2012a. Fractional purification and Biomed Anal 55:597–602. bioconversion of hemicelluloses. Biotechnol Adv 30:879–903. Pokrovskaya ID, Willett R, Smith RD, Morelle W, Kudlyk T, Lupashin VV. Peng W, Pranskevich J, Nycholat C, Gilbert M, Wakarchuk W, Paulson JC, 2011. Conserved oligomeric Golgi complex specifically regulates Razi N. 2012b. Helicobacter pylori b1,3-N-acetylglucosaminyltrans- the maintenance of Golgi glycosylation machinery. Glycobiology ferase for versatile synthesis of type 1 and type 2 poly-LacNAcs on N- 21:1554–1569. linked, O-linked and I-antigen glycans. Glycobiology 22:1453–1464. Polakova M, Belanov a M, Mikusova K, Lattova E, Perreault H. 2011. Penno MAS, Colegate SM, Michalski WP, Hoffmann P. 2012. Detection and Synthesis of 1,2,3-triazolo-linked octyl (1!6)-a-D-oligomannosides measurement of carbohydrate deficient transferrin in serum using and their evaluation in mycobacterial mannosyltransferase assay. immuno-capture mass spectrometry: Diagnostic applications for annu- Bioconjug Chem 22:289–298. al ryegrass toxicity and corynetoxin exposure. Res Vet Sci 93:611–617. PolakovaM,Sest ak S, Lattova E, Petrus L, Mucha J, Tvaroska I, Kona J. Pereira do Amaral F, Napolitano A, Masullo M, Campaner dos Santos L, 2011. a-D-Mannose derivatives as models designed for selective Festa M, Vilegas W, Pizza C, Piacente S. 2012. HPLC-ESIMSn inhibition of Golgi a-mannosidase. Eur J Med Chem 46:944–952. profiling, isolation, structural elucidation, and evaluation of the Pompach P, Chandler KB, Lan R, Edwards N, Goldman R. 2012. Semi- antioxidant potential of phenolics from Paepalanthus geniculatus.J automated identification of N-glycopeptides by hydrophilic interaction Nat Prods 75:547–556. chromatography, nano-reverse-phase LC-MS/MS, and glycan database Perrone A, Capasso A, Festa M, Kemertelidze E, Pizza C, Skhirtladze A, search. J Proteome Res 11:1728–1740. Piacente S. 2012. Antiproliferative steroidal glycosides from Digitalis Porta T, Grivet C, Knochenmuss R, Varesio E, Hopfgartner G. 2011. ciliata. Fitoterapia 83:554–562. Alternative CHCA-based matrices for the analysis of low molecular Persichetti E, Klein K, Paciotti S, Lecointe K, Balducci C, Franken S, Duvet weight compounds by UV- MALDI-tandem mass spectrometry. J Mass S, Matzner U, Roberti R, Hartmann D, Gieselmann V, Beccari T. 2012. Spectrom 46:144–152. Lysosomal di-N-acetylchitobiase-deficient mouse tissues accumulate Post DMB, Yu L, Krasity BC, Choudhury B, Mandel MJ, Brennan CA, Ruby Man2GlcNAc2 and Man3GlcNAc2. Biochim Biophys Acta 1822:1137– EG, McFall-Ngai MJ, Gibson BW, Apicella MA. 2012. O-antigen and 1146. core carbohydrate of Vibrio fischeri lipopolysaccharide. Composition Pesentseva MS, Sova VV, Sil’chenko AS, Kicha AA, Sil’chenko AS, and analysis of their role in Euprymna scolopes light organ coloniza- Haertle T, Zvyagintseva TN. 2012. A new arylsulfatase from the tion. J Biol Chem 287:8515–8530. marine mollusk Turbo chrysostomus. Chem Nat Compds 48:853– Pouilly S, Piller V, Piller F. 2012a. Metabolic glycoengineering through the 859. mammalian GalNAc salvage pathway. FEBS J 279:586–598. Petrillo M, Marinescu L, Bols M. 2011. Regioselective difunctionalization Pouilly S, Bourgeaux V, Piller F, Piller V. 2012b. Evaluation of analogues of of cyclodextrins. J Incl Phenom Macrocyclic Chem 69:425–431. GalNAc as substrates for enzymes of the mammalian GalNAc salvage Pfaff A, Barner L, Muller AHE, Granville AM. 2011. Surface modification pathway. ACS Chem Biol 7:753–760. of polymeric microspheres using glycopolymers for biorecognition. Poulin MB, Zhou R, Lowary TL. 2012. Synthetic UDP-galactofuranose Eur Polym J 47:805–815. analogs reveal critical enzyme-substrate interactions in GlfT2-cata- Phillips NJ, Adin DM, Stabb EV, McFall-Ngai MJ, Apicella MA, Gibson lyzed mycobacterial galactan assembly. Org Biomol Chem 10:4074– BW. 2011. The lipid A from Vibrio fischeri lipopolysaccharide: A 4087. unique structure bearing a phosphoglycerol moiety. J Biol Chem Pourceau G, Chevolot Y, Goudot A, Giroux F, Meyer A, Moules V, Lina B, 286:21203–21219. Cecioni S, Vidal S, Yu H, Chen X, Ferraris O, Praly J-P, Souteyrand E, Picariello G, Mamone G, Addeo F, Ferranti P. 2011. The frontiers of mass Vasseur J-J, Morvan F. 2011. Measurement of enzymatic activity and spectrometry-based techniques in food allergenomics. J Chromatogr A specificity of human and avian influenza neuraminidases from whole 1218:7386–7398. virus by glycoarray and MALDI-TOF mass spectrometry. ChemBio- Picariello G, Ferranti P, Chianese L, Addeo F. 2012. Differentiation of Vitis Chem 12:2071–2080. vinifera L. and hybrid red grapes by matrix-assisted laser desorption/ Pourcelot M, Barbier M, Landoni M, Couto S, Grand E, Kovensky J. 2011. ionization mass spectrometry analysis of berry skin anthocyanins. J Synthesis of galacturonate containing disaccharides and protein Agric Food Chem 60:4559–4566. conjugates. Curr Org Chem 15:3523–3534.

Mass Spectrometry Reviews DOI 10.1002/mas 153 & HARVEY

Pouvreau L, Jonathan MC, Kabel MA, Hinz SWA, Gruppen H, Schols HA. tion precipitation polymerization for glycopeptide enrichment. Chem 2011. Characterization and mode of action of two acetyl xylan Eur J 18:9056–9062. esterases from Chrysosporium lucknowense C1 active towards acety- Quinton L, Gilles N, Smargiasso N, Kiehne A, De Pauw E. 2011. An unusual lated xylans. Enzyme Microb Technol 49:312–320. family of glycosylated peptides isolated from Dendroaspis angusticeps Powell AK, Harvey DJ. 1996. Stabilisation of sialic acids in N-linked venom and characterized by combination of collision induced and oligosaccharides and gangliosides for analysis by positive ion matrix- electron transfer dissociation. J Am Soc Mass Spectrom 22:1891– assisted laser desorption-ionization mass spectrometry. Rapid Com- 1897. mun Mass Spectrom 10:1027–1032. Qureshi MN, Stecher G, Sultana T, Abel G, Popp M, Bonna GK. 2011. Powlesland AS, Barrio MM, Mordoh J, Hitchen PG, Dell A, Drickamer K, Determination of carbohydrates in medicinal plants-comparison be- Taylor ME. 2011. Glycoproteomic characterization of carriers of the tween TLC, mf-MELDI-MS and GC-MS. Phytochem Anal 22:296– CD15/Lewis-x epitope on Hodgkin’s Reed-Sternberg cells. BMC 302. Biochem 12: Article 13. Raessler M. 2011. Sample preparation and current applications of liquid Pozsgay V, Kubler-Kielb J, Coxon B, Santacroce P, Robbins JB, Schneerson chromatography for the determination of non-structural carbohydrates R. 2012. Synthetic oligosaccharides as tools to demonstrate cross- in plants. Trends Anal Chem 30:1833–1843. reactivity between polysaccharide antigens. J Org Chem 77:5922– Rainer M, Qureshi MN, Bonn GK. 2011. Matrix-free and material- 5941. enhanced laser desorption/ionization mass spectrometry for the analy- Prandi J. 2012. A convenient synthesis of glucose monomycolate. Carbohydr sis of low molecular weight compounds. Anal Bioanal Chem 400: Res 347:151–154. 2281–2288. Prasertsung I, Damrongsakkul S, Terashima C, Saito N, Takai O. 2012. Rajagopal MU, Hathout Y, MacDonald TJ, Kieran MW, Gururangan S, Preparation of low molecular weight chitosan using solution plasma Blaney SM, Phillips P, Packer R, Gordish-Dressman H, Rood BR. system. Carbohydr Polym 87:2745–2749. 2011. Proteomic profiling of cerebrospinal fluid identifies prostaglan- Prashar D, Cui D, Bandyopadhyay D, Luk Y-Y. 2011. Modification of din D2 synthase as a putative biomarker for pediatric medulloblastoma. proteins with cyclodextrins prevents aggregation and surface adsorp- A pediatric brain tumor consortium study. Proteomics 11:935–943. tion and increases thermal stability. Langmuir 27:13091–13096. Rajakumar P, Anandhan R. 2011. Synthesis and in-vitro anti-inflammatory Price NPJ, Naumann TA. 2011. A high-throughput matrix-assisted laser activity of novel glycodendrimers with benzene 1,3,5-carboxamide desorption/ionization-time-of-flight mass spectrometry-based assay of core and triazole as branching unit. Eur J Med Chem 46:4687–4695. chitinase activity. Anal Biochem 411:94–99. Raju TS, Jordan RE. 2012. Galactosylation variations in marketed therapeu- Price NPJ, Hartman TM, Faber TA, Vermillion KE, Fahey GCJ. 2011. tic antibodies. mAbs 4:385–391. Galactoglucomannan oligosaccharides (GGMO) from a molasses Raju TS, Knight DM, Jordan RE. 2011. Glyco-engineering of Fc glycans to byproduct of pine (Pinus taeda) fiberboard production. J Agric Food enhance the biological functions of therapeutic IgGs. In: Owens RJ, Chem 59:1854–1861. Nettleship JE, editors. Functional and structural proteomics of Price NPJ, Ray KJ, Vermillion KE, Dunlap CA, Kurtzman CP. 2012. glycoproteins. Dordrecht: Springer. pp. 39–58. Structural characterization of novel sophorolipid biosurfactants from a Rakosi K, Szolomajer-Csikos O, Kalmar L, Szurmai Z, KerekgyartoJ,T oth newly identified species of Candida yeast. Carbohydr Res 348:33–41. GK. 2011. Synthesis of N-glycopeptides applying glycoamino acid Prinsep MR, Puddick J. 2011. Laser desorption ionisation-time of flight building blocks with a combined Fmoc/Boc strategy. Protein Peptide mass spectrometry of the tolyporphins, bioactive metabolites from Lett 18:679–683. the cyanobacterium Tolypothrix nodosa. Phytochem Anal 22:285– Rakus JF, Mahal LK. 2011. New technologies for glycomic analysis: Toward 290. a systematic understanding of the glycome. Annu Rev Anal Chem Pruitt RN, Chumbler NM, Rutherford SA, Farrow MA, Friedman DB, 4:367–392. Spiller B, Lacy DB. 2012. Structural determinants of Clostridium Ralet M-C, Williams MAK, Tanhatan-Nasseri A, Ropartz D, Quemener B, difficile toxin A glucosyltransferase activity. J Biol Chem 287:8013– Bonnin E. 2012. Innovative enzymatic approach to resolve homoga- 8020. lacturonans based on their methylesterification pattern. Biomacromo- Przybylski C, Jarroux N. 2011. Analysis of a polydisperse polyrotaxane lecules 13:1615–1624. based on poly(ethylene oxide) and a-cyclodextrins using nanoelectros- Ramakrishnan B, Boeggeman E, Pasek M, Qasba PK. 2011. Bioconjugation pray and LTQ- orbitrap. Anal Chem 83:8460–8467. using mutant glycosyltransferases for the site-specific labeling of Przybylski C, Blin F, Jarroux N. 2011. Toward a more accurate structural biomolecules with sugars carrying chemical handles. Methods Mol determination of high molecular weight polyrotaxanes based on Biol 751:281–296. cyclodextrins by MALDI-TOF MS. Macromolecules 44:1821–1830. Ramakrishnan B, Boeggeman E, Qasba PK. 2012. Binding of N-acetylglu- Pucic M, Knezevic A, Vidic J, Adamczyk B, Novokmet M, Polasek O, cosamine (GlcNAc) b1-6-branched oligosaccharide acceptors to b4- Gornik O, Supraha-Goreta S, Wormald MR, Redzic I, Campbell H, galactosyltransferase I reveals a new ligand binding mode. J Biol Chem Wright A, Hastie ND, Wilson JF, Rudan I, Wuhrer M, Rudd PM, Josic 287:28666–28674. D, Lauc G. 2011. High throughput isolation and glycosylation analysis Ranzinger R, Herget S, von der Lieth C-W, Frank M. 2011. GlycomeDB-a of IgG. Variability and heritability of the IgG glycome in three isolated unified database for carbohydrate structures. Nucleic Acids Res 39: human populations. Mol Cell Proteomics 10:M110.004700. D373–D376. Purushotham P, Podile AR. 2012. Synthesis of long-chain chitooligosacchar- Rao V, Alleti R, Xu L, Tafreshi NK, Morse DL, Gillies RJ, Mash EA. 2011. ides by a hypertransglycosylating processive endochitinase of Serratia A sucrose-derived scaffold for multimerization of bioactive peptides. proteamaculans 568. J Bacteriol 194:4260–4271. Bioorg Med Chem 19:6474–6482. Qian Y, Zhang X, Zhou L, Yun X, Xie J, Xu J, Ruan Y, Ren S. 2012. Site- Rathjens A, Thiem J. 2011. Synthesis of carbohydrate-based azamacrocycles specific N-glycosylation identification of recombinant human lectin- by Richman-Atkins cyclisation. C R Chimie 14:286–300. like oxidized low density lipoprotein receptor-1 (LOX-1). Glycoconj J Raymond C, Robotham A, Kelly J, Lattova E, Perreault H, Durocher Y. 29:399–409. 2012. Production of highly sialylated monoclonal antibodies. In: Qin H, Zhao L, Li R, Wu R, Zou H. 2011. Size-selective enrichment of N- Petrescu S, editor. Glycosylation. Rijeka, Croatia: InTech. pp. 397– linked glycans using highly ordered mesoporous carbon material and 418. detection by MALDI-TOF MS. Anal Chem 83:7721–7728. Rebecchi K, Woodin C, Desaire H. 2011a. Recent mass spectrometric based Qu Y, Liu J, Yang K, Liang Z, Zhang L, Zhang Y. 2012. Boronic acid methods in quantitative N-linked glycoproteomics. Curr Proteomics functionalized core-shell polymer nanoparticles prepared by distilla- 8:269–277.

154 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Rebecchi KR, Go EP, Xu L, Woodin CL, Mure M, Desaire H. 2011b. A tions: Towards profiling glycoproteins without labeling or liberation general protease digestion procedure for optimal protein sequence steps. Chem Soc Rev 41:5744–5779. coverage and post-translational modifications analysis of recombinant Rhee J-K, Baksh M, Nycholat C, Paulson JC, Kitagishi H, Finn MG. 2012. glycoproteins: Application to the characterization of human lysyl Glycan-targeted virus-like nanoparticles for photodynamic therapy. oxidase-like 2 glycosylation. Anal Chem 83:8484–8491. Biomacromolecules 13:2333–2338. Rebuffet E, Groisillier A, Thompson A, Jeudy A, Barbeyron T, Czjzek M, Richards AL, Lietz CB, Wager-Miller J, Mackie K, Trimpin S. 2012. Michel G. 2011. Discovery and structural characterization of a novel Localization and imaging of gangliosides in mouse brain tissue glycosidase family of marine origin. Environ Microbiol 13:1253–1270. sections by laserspray ionization inlet. J Lipid Res 53:1390–1398. Rech C, Rosencrantz RR, Krenek K, Pelantova H, BojarovaP,Romer€ CE, Rieder A, Grimmer S, Aachmann FL, Westereng B, Kolset SO, Knutsen SH. Hanisch F-G, Kren V, Ellinga L. 2011. Combinatorial one-pot synthesis 2012. Generic tools to assess genuine carbohydrate specific effects on of poly-N-acetyllactosamine oligosaccharides with Leloir-glycosyl- in vitro immune modulation exemplified by b-glucans. Carbohydr transferases. Adv Synth Catal 353:2492–2500. Polym 92:2075–2083. Reddy KC, Padmaja N, Pathak V, Pathak AK. 2012. Concise synthesis of an arabinofuranose hexasaccharide present in the cell wall of Mycobacte- Rillahan CD, Antonopoulos A, Lefort CT, Sonon R, Azadi P, Ley K, Dell A, rium tuberculosis. Tetrahedron Lett 53:2461–2464. Haslam SM, Paulson JC. 2012. Global metabolic inhibitors of sialyl- and fucosyltransferases remodel the glycome. Nat Chem Biol 8:661– Redelinghuys P, Antonopoulos A, Liu Y, Campanero-Rhodes MA, McKen- 668. zie E, Haslam SM, Dell A, Feizi T, Crocker PR. 2011. Early murine T- lymphocyte activation is accompanied by a switch from N-glycolyl- to Rivas S, Gullon B, Gullon P, Alonso JL, Parajo JC. 2012. Manufacture and N-acetyl-neuraminic acid and generation of ligands for siglec-E. J Biol properties of bifidogenic saccharides derived from wood mannan. J Chem 286:34522–34532. Agric Food Chem 60:4296–4305. Regulski K, Courtin P, Meyrand M, Claes IJJ, Lebeer S, Vanderleyden J, Robinson LN, Artpradit C, Raman R, Shriver ZH, Ruchirawat M, Hols P, Guillot A, Chapot-Chartier M-P. 2012. Analysis of the Sasisekharan R. 2012. Harnessing glycomics technologies: Integrating peptidoglycan hydrolase complement of Lactobacillus casei and structure with function for glycan characterization. Electrophoresis characterization of the major g-D-glutamyl-L-ysyl-endopeptidase. 33:797–814. PLoS One 7:e32301. Rockova S, Nevoral J, Rada V, Marsik P, Sklenar J, Hinkova A, Vlkova E, Reichelt S, Elsner C, Prager A, Naumov S, Kuballa J, Buchmeiser MR. Marounek M. 2011. Factors affecting the growth of bifidobacteria in 2012. Amino-functionalized monolithic spin-type columns for high- human milk. Int Dairy J 21:504–508. throughput lectin affinity chromatography of glycoproteins. Analyst Rodriguez-Colinas B, de Abreu MA, Fernandez-Arrojo L, de Beer R, Poveda 137:2600–2607. A, Jimenez-Barbero J, Haltrich D, Ballesteros AO, Fernandez-Lobato Reid EM, Vigneau ES, Gratia SS, Marzabadi CH, De Castro M. 2012. One- M, Plou FJ. 2011. Production of galacto-oligosaccharides by the b- pot synthesis of N-glycooxazolines, N-glycoaminooxazolines, and N- galactosidase from Kluyveromyces lactis: Comparative analysis of glycothiazolines from glycals. Eur J Org Chem 3295–3303. permeabilized cells versus soluble enzyme. J Agric Food Chem 59:10477–10484. Reindl W, Deng K, Gladden JM, Cheng G, Wong A, Singer SW, Singh S, Lee J-C, Yao C-H, Hazen TC, Singh AK, Simmons BA, Adams PD, Rodriguez-Colinas B, Poveda A, Jimenez-Barbero J, Ballesteros AO, Plou Northen TR. 2011. Colloid-based multiplexed screening for plant FJ. 2012. Galacto-oligosaccharide synthesis from lactose solution or biomass-degrading glycoside hydrolase activities in microbial commu- skim milk using the b-galactosidase from Bacillus circulans. J Agric nities. Energy Environ Sci 4:2884–2893. Food Chem 60:6391–6398. Reines M, Llobet E, Llompart CM, Moranta D, Perez-Gutierrez C, Rodriguez-Jasso RM, Mussatto SI, Pastrana L, Aguilar CN, Teixeira JA. Bengoechea JA. 2012a. Molecular basis of Yersinia enterocolitica 2011. Microwave-assisted extraction of sulfated polysaccharides temperature-dependent resistance to antimicrobial peptides. J Bacteriol (fucoidan) from brown seaweed. Carbohydr Polym 86:1137–1144. 194:3173–3188. Rohmer M, Meyer B, Mank M, Stahl B, Bahr U, Karas M. 2010. Reines M, Llobet E, Dahlstrom€ KM, Perez-Gutierrez C, Llompart CM, 3-Aminoquinoline acting as matrix and derivatizing agent for MALDI Torrecabota N, Salminen TA, Bengoechea JA. 2012b. Deciphering the MS analysis of oligosaccharides. Anal Chem 82:3719–3726. acylation pattern of Yersinia enterocolitica Lipid A. PLoS Pathog 8: Rohmer M, Baeumlisberger D, Stahl B, Bahr U, Karas M. 2011. Fragmenta- e1002978. tion of neutral oligosaccharides using the MALDI LTQ Orbitrap. Int J Reinke SO, Bayer M, Berger M, Blanchard V, Hinderlich S. 2011. Analysis Mass Spectrom 305:199–208. of cell surface N-glycosylation of the human embryonic kidney 293T Rolain T, Bernard E, Courtin P, Bron PA, Kleerebezem M, Chapot- cell line. J Carbohydr Chem 30:218–232. Chartier M-P, Hols P. 2012. Identification of key peptidoglycan Reinke SO, Bayer M, Berger M, Hinderlich S, Blanchard V. 2012. The hydrolases for morphogenesis, autolysis, and peptidoglycan composi- analysis of N-glycans of cell membrane proteins from human tion of Lactobacillus plantarum WCFS1. Microb Cell Factories 11: hematopoietic cell lines reveals distinctions in their pattern. Biol Chem Article 137. 393:731–747. Rombouts Y, Alibaud L, Carrere-Kremer S, Maes E, Tokarski C, Elass E, Remmerie N, De Vijlder T, Laukens K, Dang TH, Lemiere F, Mertens I, Kremer L, Guerardel Y. 2011. Fatty acyl chains of Mycobacterium Valkenborg D, Blust R, Witters E. 2011. Next generation functional marinum lipooligosaccharides. Structure, localization and acylation by proteomics in non-model plants: A survey on techniques and applica- PapA4 (MMAR_2343) protein. J Biol Chem 286:33678–33688. tions for the analysis of protein complexes and post-translational Rombouts Y, Brust B, Ojha AK, Maes E, Coddeville B, Elass-Rochard E, modifications. Phytochemistry 72:1192–1218. Kremer L, Guerardel Y. 2012. Exposure of mycobacteria to cell wall- Ren JM, Wiltshire JT, Blencowe A, Qiao GG. 2011. Synthesis of a star inhibitory drugs decreases production of arabinoglycerolipid related to polymer library with a diverse range of highly functionalized mycolyl-arabinogalactan-peptidoglycan metabolism. J Biol Chem macromolecular architectures. Macromolecules 44:3189–3202. 287:11060–11069. Ren G, Hou J, Fang Q, Sun H, Liu X, Zhang L, Wang PG. 2012a. Synthesis Romero- Ramrez L, Garca-Alvarez I, Campos-Olivas R, Gilbert M, Goneau of flavonol 3-O-glycoside by UGT78D1. Glycoconj J 29:425–432. M-F, Fernandez-Mayoralas A, Nieto-Sampedro M. 2012. Specific Ren S, Chen Q, Ding N, Zhang W, Li Y, Guo Y. 2012b. Synthesis and synthesis of neurostatin and gangliosides O-acetylated in the outer biological evaluation of analogs of methyl ursolate 3-O-b-chacotrio- sialic acids using a sialate transferase. PLoS One 7:e49983. side as H5N1 viral entry inhibitors. J Carbohydr Chem 31:647–658. Ronholm J, Wang L, Hayashi I, Sugai M, Zhang Z, Cao X, Lin M. 2012. The Reuel NF, Mu B, Zhang J, Hinckley A, Strano MS. 2012. Nanoengineered Listeria monocytogenes serotype 4b autolysin IspC has N-acetylgluco- glycan sensors enabling native glycoprofiling for medicinal applica- saminidase activity. Glycobiology 22:1311–1320.

Mass Spectrometry Reviews DOI 10.1002/mas 155 & HARVEY

Ropartz D, Bodet P-E, Przybylski C, Gonnet F, Daniel R, Fer M, Helbert W, Saito M, Mylvaganum M, Tam P, Novak A, Binnington B, Lingwood C. Bertrand D, Rogniaux H. 2011. Performance evaluation on a wide set 2012a. Structure-dependent pseudoreceptor intracellular traffic of of matrix-assisted laser desorption ionization matrices for the detection adamantyl globotriaosyl ceramide mimics. J Biol Chem 287:16073– of oligosaccharides in a high-throughput mass spectrometric screening 16087. of carbohydrate depolymerizing enzymes. Rapid Commun Mass Saito N, Nakamura M, Shinoda K, Murata N, Kanazawa T, Kato K, Toki K, Spectrom 25:2059–2070. Kasai H, Honda T, Tatsuzawa F. 2012b. Covalent anthocyanin-flavonol Rosenberger AFN, Hangelmann L, Hofinger A, Wilson IBH. 2012. UDP- complexes from the violet-blue flowers of Allium ’Blue Perfume’. xylose and UDP-galactose synthesis in Trichomonas vaginalis. Mol Phytochemistry 80:99–108. Biochem Parasitol 181:53–56. Saito Y, Waki M, Hameed S, Hayasaka T, Setou M. 2012c. Development of Rosengren A, H€agglund P, Anderson L, Pavon-Orozco P, Peterson-Wulff R, imaging mass spectrometry. Biol Pharm Bull 35:1417–1424. Nerinckx W, Sta˚lbrand H. 2012. The role of subsite þ2 of the Salinas PA, Miller MJC, Lin MX, Savickas PJ, Thomas JJ. 2012. Mass Trichoderma reesei b-mannanase TrMan5A in hydrolysis and trans- spectrometry-based characterization of acidic glycans on protein glycosylation. Biocatal Biotransfor 30:338–352. therapeutics. Int J Mass Spectrom 312:122–134. Roux R, Sallet L, Alcouffe P, Chambert S, Sintes-Zydowicz N, Fleury E, Samanta S, Dutta D, Ghoshal A, Mukhopadhyay S, Saha B, Sundar S, Bernard J. 2012. Facile and rapid access to glyconanocapsules by Jarmalavicius S, Forgber M, Mandal C, Walden P, Mandal C. 2011. CuAAC interfacial polyaddition in miniemulsion conditions. ACS Glycosylation of erythrocyte spectrin and its modification in visceral Macro Lett 1:1074–1078. leishmaniasis. PLoS One 6:e28169. Rozema E, Popescu R, Sonderegger H, Huck CW, Winkler J, Krupitza G, Sampedro J, Gianzo C, Iglesias N, Guitian E, Revilla G, Zarra I. 2012. Urban E, Kopp B. 2012. Characterization of glucocerebrosides and the AtBGAL10 Is the main xyloglucan b-galactosidase in Arabidopsis, active metabolite 4,8-sphingadienine from Arisaema amurense and and its absence results in unusual xyloglucan subunits and growth Pinellia ternata by NMR and CD spectroscopy and ESI-MS/CID-MS. defects. Plant Physiol Biochem 158:1146–1157. J Agric Food Chem 60:7204–7210. ~ Sanchez-Navarro M, Munoz A, Illescas BM, Rojo J, Martn N. 2011. Rubio-Moraga A, Gerwig GJ, Castro-Daz N, Jimeno ML, Escribano J, Fullerene as multivalent scaffold: Efficient molecular recognition of Fernandez J-A, Kamerling JP. 2011. Triterpenoid saponins from corms globular glycofullerenes by concanavalin A. Chem Eur J 17:766–769. Crocus sativus of : Localization, extraction and characterization. Ind Sanchez-Pomales G, Morris TA, Falabella JB, Tarlov MJ, Zangmeister RA. Crops Prod 34:1401–1409. 2012. A lectin-based gold nanoparticle assay for probing glycosylation Ruhaak LR, Huhn C, Koeleman CAM, Deelder AM, Wuhrer M. 2012. of glycoproteins. Biotechnol Bioeng 109:2240–2249. Robust and high-throughput sample preparation for (semi-) quantita- Sanchez-Ruiz A, Serna S, Ruiz N, Martin-Lomas M, Reichardt N-C. 2011. tive analysis of N-glycosylation profiles from plasma samples. MALDI-TOF Mass spectrometric analysis of enzyme activity and Methods Mol Biol 893:371–385. lectin trapping on an array of N-glycans. Angew Chem Int Ed 50:1801– Ruhaak LR, Lebrilla CB. 2012a. Analysis and role of oligosaccharides in 1804. milk. BMB Reports 45:442–451. Sanchez EJ, Lewis KM, Munske GR, Nissen MS, Kang C. 2012. Glycosyla- Ruhaak LR, Lebrilla CB. 2012b. Advances in analysis of human milk tion of skeletal calsequestrin: Implications for its function. J Biol oligosaccharides. Adv Nutr 3:406S–414S. Chem 287:3042–3050. Ruiz-Matute AI, Brokl M, Sanz ML, Soria AC, Cot^ e GL, Collins ME, Rastall Sano M, Korekane H, Ohtsubo K, Yamaguchi Y, Kato M, Shibukawa Y, RA. 2011. Effect of dextransucrase cellobiose acceptor products on the Tajiri M, Adachi H, Wada Y, Asahi M, Taniguchi N. 2012. N-Glycans growth of human gut bacteria. J Agric Food Chem 59:3693–3700. of SREC-I (scavenger receptor expressed by endothelial cells): Ruiz-May E, Thannhauser TW, Zhang S, Rose JKC. 2012. Analytical Essential role for ligand binding, trafficking and stability. Glycobiol- technologies for identification and characterization of the plant N- ogy 22:714–724. glycoproteome. Front Plant Sci 3: Article 150. Santelia D, Kotting€ O, Seung D, Schubert M, Thalmann M, Bischof S, Ryan CM, Mehlert A, Richardson JM, Ferguson MAJ, Johnson PJ. 2011. Meekins DA, Lutz A, Patron N, Gentry MS, Allain FH-T, Zeeman Chemical structure of Trichomonas vaginalis surface lipoglycan. A SC. 2011. The phosphoglucan phosphatase like sex four2 dephosphor- role for short galactose (b1-4/3) N-acetyl glucosamine repeats in host ylates starch at the C3-position in Arabidopsis. Plant Cell 23:4096– cell interaction. J Biol Chem 286:40494–40508. 4111. Ryan DA, Rebek JJ. 2011. A carbohydrate-conjugated deep cavitand permits Santra A, Misra AK. 2012. Convergent synthesis of the pentasaccharide observation of caviplexes in human serum. J Am Chem Soc repeating unit of the O-antigenic polysaccharide of enterohaemorrha- 133:19653–19655. gic Escherichia coli O113. Glycoconj J 29:181–188. Saadatmand S, Edlund U, Albertsson A-C, Danielsson S, Dahlman O. 2012. Prehydrolysis in softwood pulping produces a valuable biorefinery Santra A, Ghosh T, Misra AK. 2012. Expedient synthesis of two structurally fraction for material utilization. Environ Sci Technol 46:8389–8396. close tetrasaccharides corresponding to the O-antigens of Escherichia coli O127 and Salmonella enterica O13. Tetrahedron Asym 23:1385– Sabatte J, Faigle W, Ceballos A, Morelle W, Rodrgues CR, Lenicov FR, 1392. Thepaut M, Fieschi F, Malchiodi E, Fernandez M, Arenzana-Seisdedos F, Lortat-Jacob H, Michalski J-C, Geffner J, Amigorena S. 2011. Sarabia-Sainz A-I, Ramos-Clamont G, Winzerling J, Vazquez-Moreno L. Semen clusterin is a novel DC-SIGN ligand. J Immunol 187:5299– 2011. Bacterial recognition of thermal glycation products derived 5309. from porcine serum albumin with lactose. Acta Biochim Polon 58:95– 100. Safina G. 2012. Application of surface plasmon resonance for the detection of carbohydrates, glycoconjugates, and measurement of the carbohy- Sardzk R, Sharma R, Kaloo S, Voglmeir J, Crocker PR, Flitsch SL. 2011. drate-specific interactions: A comparison with conventional analytical Chemoenzymatic synthesis of sialooligosaccharides on arrays for techniques. A critical review. Anal Chim Acta 712:9–29. studies of cell surface adhesion. Chem Commun 47:5425–5427. Saikam V, Raghupathy R, Yadav M, Gannedi V, Singh PP, Qazi NA, Sawant S9ardzk R, Green AP, Laurent N, Both P, Fontana C, Voglmeir J, Weissenborn SD, Vishwakarma RA. 2011. Synthesis of new fluorescently labeled MJ, Haddoub R, Grassi P, Haslam SM, Widmalm G, Flitsch SL. 2012. glycosylphosphatidylinositol (GPI) anchors. Tetrahedron Lett 52: Chemoenzymatic synthesis of O-mannosylpeptides in solution and on 4277–4279. solid phase. J Am Chem Soc 134:4521–4524. Saito K, Hamano K, Nakagawa M, Yugawa K, Muraoka J, Kuba H, Sarkar D, Sidhu M, Singh A, Chen J, Lammas DA, van der Sar AM, Besra Furukawa K, Azuma T. 2011. Conformational analysis of human serum GS, Bhatt A. 2011. Identification of a glycosyltransferase from albumin and its non-enzymatic glycation products using monoclonal Mycobacterium marinum involved in addition of a caryophyllose antibodies. J Biochem (Tokyo) 149:569–580. moiety in lipooligosaccharides. J Bacteriol 193:2336–2340.

156 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Sarsby J, Towers MW, Stain C, Cramer R, Koroleva OA. 2012. Mass Schwarz F, Lizak C, Fan Y-Y, Fleurkens S, Kowarik M, Aebi M. 2011b. spectrometry imaging of glucosinolates in Arabidopsis flowers and Relaxed acceptor site specificity of bacterial oligosaccharyltransferase siliques. Phytochemistry 77:110–118. in vivo. Glycobiology 21:45–54. Sarver SA, Keithley RB, Essaka DC, Tanaka H, Yoshimura Y, Palcic MM, Scott A, Weldon S, Buchanan PJ, Schock B, Ernst RK, McAuley DF, Hindsgaul O, Dovichi NJ. 2012. Preparation and electrophoretic Tunney MM, Irwin CR, Elborn S, Taggart CC. 2011. Evaluation of the separation of Bodipy-Fl-labeled glycosphingolipids. J Chromatogr A ability of LL-37 to neutralise LPS in vitro and ex vivo. PLoS One 6: 1229:268–273. e26525. Satoh H, Yamauchi T, Yamasaki M, Maede Y, Yabuki A, Chang H-S, Sebestik J, Niederhafner P, Jezek J. 2011. Peptide and glycopeptide Asanuma T, Yamato O. 2011. Rapid detection of GM1 ganglioside in dendrimers and analogous dendrimeric structures and their biomedical cerebrospinal fluid in dogs with GM1 gangliosidosis using matrix- applications. Amino Acids 40:301–370. assisted laser desorption ionization time-of-flight mass spectrometry. J Sedo O, Marova I, Zdrahal Z. 2012. Beer fingerprinting by matrix- assisted Vet Diagn Invest 23:1202–1207. laser desorption-ionisation-time of flight mass spectrometry. Food Sau A, Misra AK. 2012. Convergent synthesis of the tetrasaccharide Chem 135:473–478. repeating unit of the cell wall lipopolysaccharide of Escherichia coli Sehgal P, Kumar O, Kameswararao M, Ravindran J, Khan M, Sharma S, O40. Beilstein J Org Chem 8:2053–2059. Vijayaraghavan R, Prasad GBKS. 2011. Differential toxicity profile of Savran T, Gulcemal€ D, Masullo M, Karayldrm T, Polat E, Piacente S, ricin isoforms correlates with their glycosylation levels. Toxicol Alankus-S CalS skanS O.€ 2012. Cycloartane glycosides from Astragalus Mechanisms Meth 282:56–67. erinaceus. Rec Nat Prod 6:230–236. Sekiya S, Taniguchi K, Tanaka K. 2012. On-target separation of analyte with S€awen E, Ostervall€ J, Landersjo€ C, Edblad M, Weintraub A, Ansaruzzaman 3-aminoquinoline/a-cyano-4-hydroxycinnamic acid liquid matrix for M, Widmalm G. 2012. Structural studies of the O-antigenic polysac- matrix-assisted laser desorption/ionization mass spectrometry. Rapid charide from Plesiomonas shigelloides strain AM36565. Carbohydr Commun Mass Spectrom 26:693–700. Res 348:99–103. Sela DA, Li Y, Lerno L, Wu S, Marcobal AM, German JB, Chen X, Lebrilla Schiel JE. 2012. Glycoprotein analysis using mass spectrometry: Unraveling CB, Mills DA. 2011. An infant-associated bacterial commensal utilizes the layers of complexity. Anal Bioanal Chem 404:1141–1149. breast milk sialyloligosaccharides. J Biol Chem 286:11909–11918. Schiel JE, Au J, He H-J, Phinney KW. 2012. LC-MS/MS biopharmaceutical Sela DA, Garrido D, Lerno L, Wu S, Tan K, Eom H-J, Joachimiak A, Lebrilla glycoanalysis: Identification of desirable reference material character- CB, Mills DA. 2012. Bifidobacterium longum subsp. infantis ATCC istics. Anal Bioanal Chem 403:2279–2289. 15697 a-fucosidases are active on fucosylated human milk oligosac- Schierholt A, Hartmann M, Lindhorst TK. 2011. Bi- and trivalent glycopep- charides. Appl Environ Microbiol 78:795–803. tide mannopyranosides as inhibitors of type 1 fimbriae-mediated Selman MHJ, Hemayatkar M, Deelder AM, Wuhrer M. 2011a. Cotton bacterial adhesion: variation of valency, aglycon and scaffolding. HILIC SPE microtips for microscale purification and enrichment of Carbohydr Res 346:1519–1526. glycans and glycopeptides. Anal Chem 83:2492–2499. Schiller J, Fuchs B, Teuber K, Nimptsch A, Nimptsch K, Rosmarie S. 2011. Selman MHJ, Niks EH, Titulaer MJ, Verschuuren JJGM, Wuhrer M, Deelder TLC/HPTLC with direct mass spectrometric detection: A review of the AM. 2011b. IgG Fc N-glycosylation changes in Lambert-Eaton progress achieved in the last 5 years. In: Srivastava MM, editor. High- myasthenic syndrome and myasthenia gravis. J Proteome Res 10:143– performance thin-layer chromatography (HPTLC). Berlin: Springer- 152. Verlag. pp. 335–363. Selman MHJ, Hoffmann M, Zauner G, McDonnell LA, Balog CIA, Rapp E, Schiller B, Makrypidi G, Razzazi-Fazeli E, Paschinger K, Walochnik Deelder AM, Wuhrer M. 2012. MALDI-TOF-MS analysis of sialylated J, Wilson IBH. 2012. Exploring the unique N-glycome of the glycans and glycopeptides using 4-chloro-a-cyanocinnamic acid opportunistic human pathogen Acanthamoeba. J Biol Chem 287: matrix. Proteomics 12:1337–1348. 43191–43204. Schjoldager KT-BG, Vester-Christensen MB, Goth CK, Petersen TN, Brunak Seneviratne C, Dombi GW, Liu W, Dain JA. 2011. The in vitro glycation of S, Bennett EP, Levery SB, Clausen H. 2011. A systematic study of site- human serum albumin in the presence of Zn(II). J Inorg Biochem specific GalNAc-type O-glycosylation modulating proprotein conver- 105:1548–1554. tase processing. J Biol Chem 286:40122–40132. Seneviratne C, Dombi GW, Liu W, Dain JA. 2012. In vitro glycation of Schjoldager KT-BG, Vakhrushev SY, Kong Y, Steentoft C, Nudelman AS, human serum albumin by dihydroxyacetone and dihydroxyacetone Pedersen NB, Wandall HH, Mandel U, Bennett EP, Levery SB, Clausen phosphate. Biochem Biophys Res Commun 417:817–823. H. 2012. Probing isoform-specific functions of polypeptide GalNAc- Seo YS, Shin K-S. 2011. Optimal conditions and substrate specificity for transferases using zinc finger nuclease glycoengineered SimpleCells. trehalose production by resting cells of Arthrobacter crystallopoietes Proc Natl Acad Sci USA 109:9893–9898. n-08. J Food Sci Nutrit 16:357–363. Schlegel MK, Hutter€ J, Eriksson M, Lepenies B, Seeberger PH. 2011. Seo JH, Kim CS, Lee HY, Kawai T, Cha HJ. 2011a. Interactive configuration Defined presentation of carbohydrates on a duplex DNA scaffold. through force analysis of GM1 pentasaccharide-Vibrio cholera toxin ChemBioChem 12:2791–2800. interaction. Anal Chem 83:6011–6017. Schlick KH, Morgan JR, Weiel JJ, Kelsey MS, Cloninger MJ. 2011. Clusters Seo S-H, Choi K-H, Hwang S, Kim J, Park C-S, Rho J-R, Cha J. 2011b. of ligands on dendrimer surfaces. Bioorg Med Chem Lett 21:5078– Characterization of the catalytic and kinetic properties of a thermosta- 5083. ble Thermoplasma acidophilum a-glucosidase and its transglucosyla- Schnueriger A, Grau R, Sondermann P, Schreitmueller T, Marti S, Zocher M. tion reaction with arbutin. J Mol Catal B Enzymatic 72:305–312. 2011. Development of a quantitative, cell-line based assay to measure Seo JH, Lee HY, Cha HJ. 2012. Characterization of the GM1 pentasacchar- ADCC activity mediated by therapeutic antibodies. Mol Immunol ide-Vibrio cholera toxin interaction using a carbohydrate-based 48:1512–1517. electrochemical system. Analyst 137:2860–2865. Schonbeck€ C, Westh P, Madsen JC, Larsen KL, St€ade LW, Holm R. 2011. Serna S, Yan S, Martin-Lomas M, Wilson IBH, Reichardt N-C. 2011. Methylated b-cyclodextrins: Influence of degree and pattern of Fucosyltransferases as synthetic tools: Glycan array based substrate substitution on the thermodynamics of complexation with tauro- and selection and core fucosylation of synthetic N-glycans. J Am Chem Soc glyco- conjugated bile salts. Langmuir 27:5832–5841. 133:16495–16502. Schwarz F, Fan Y-Y, Schubert M, Aebi M. 2011a. Cytoplasmic N- Serrato RV, Balsanelli E, Sassaki GL, Carlson RW, Muszynski A, Monteiro glycosyltransferase of Actinobacillus pleuropneumoniae is an inverting RA, Pedrosa FO, Souza EM, Iacomini M. 2012. Structural analysis of enzyme and recognizes the NX(S/T) consensus sequence. J Biol Chem Herbaspirillum seropedicae lipid-A and of two mutants defective to 286:35267–35274. colonize maize roots. Int J Biol Macromol 51:384–391.

Mass Spectrometry Reviews DOI 10.1002/mas 157 & HARVEY

Seviour T, Yuan Z, van Loosdrecht MCM, Lin Y. 2012. Aerobic sludge from the sea cucumber Eupentacta fraudatrix and its biosynthetic granulation: A tale of two polysaccharides?. Water Res 46:4803–4813. significance. Biochem System Ecol 44:53–60. Shaikh AY, Sureshkumar G, Pati D, Gupta SS, Hotha S. 2011. Facile Silipo A, Sturiale L, Perino V, Garozzo D, Lanzetta R, Parrilli M, Molinaro synthesis of unusual glycosyl carbamates and amino acid glycosides A. 2010. The structure of the carbohydrate backbone of the lip- from propargyl 1,2-orthoesters as glycosyl donors. Org Biomol Chem ooligosaccharide from the halophilic bacterium Arcobacter halophilus. 9:5951–5959. Carbohydr Res 345:850–853. Sharipova RR, Strobykina IY, Mordovskoi GG, Chestnova RV, Mironov VF, Silipo A, Sturiale L, De Castro C, Lanzetta R, Parrilli M, Garozzo D, Kataev VE. 2011. Antituberculosis activity of glycosides from Stevia Molinaro A. 2012. Structure of the lipopolysaccharide isolated from rebaudiana and hybrid compounds of steviolbioside and pyridinecar- the novel species Uruburuella suis. Carbohydr Res 357:75–82. boxylic acid hydrazides. Chem Nat Compds 46:902–905. Silva GB, Ionashiro M, Carrara TB, Crivellari AC, Tine MAS, Prado J, Sheng X, Nakajima T, Wang L, Zhang X, Kamijo Y, Takahashi K, Tanaka N, Carpita NC, Buckeridge MS. 2011. Cell wall polysaccharides from Sugiyama E, Kyogashima M, Aoyama T, Hara A. 2012. Attenuation of fern leaves: Evidence for a mannan-rich Type III cell wall in Adiantum kidney injuries maintains serum sulfatide levels dependent on hepatic raddianum. Phytochem Lett 72:2352–2360. synthetic vbility: A possible involvement of oxidative stress. Tohoku J Simoes~ J, Nunes FM, Domingues P, Coimbra MA, Domingues MR. 2012. Exp Med 227:1–12. Mass spectrometry characterization of an Aloe vera mannan presenting Shepherd MD, Liu T, Mendez C, Salas JA, Rohr J. 2011. Engineered immunostimulatory activity. Carbohydr Polym 90:229–236. biosynthesis of gilvocarcin analogues with altered deoxyhexopyranose Sim unek J, Brandysova V, KoppovaI,Sim unek J, Jr. 2012. The antimicrobial moieties. Appl Environ Microbiol 777:435–441. action of chitosan, low molar mass chitosan, and chitooligosaccharides Shi C, Meng J, Deng C. 2012a. Facile synthesis of magnetic graphene and on human colonic bacteria. Folia Microbiol 57:341–345. carbon nanotube composites as a novel matrix and adsorbent for Singh RP, Shukla MK, Mishra A, Kumari P, Reddy CRK, Jha B. 2011a. enrichment and detection of small molecules by MALDI-TOF MS. J Isolation and characterization of exopolysaccharides from seaweed Mater Chem 22:20778–20785. associated bacteria Bacillus licheniformis. Carbohydr Polym 84:1019– Shi F, Harada T, Ogawa Y, Ono H, Ohnishi-Kameyama M, Miyamoto T, 1026. Eguchi M, Shimoji Y. 2012b. Capsular polysaccharide of Erysipelo- Singh S, Andersen MT, Steen JJ. 2011b. The application of high throughput thrix rhusiopathiae, the causative agent of swine erysipelas, and its mass spectrometry to the analysis of glycoproteins. In: Owens RJ, modification with phosphorylcholine. Infect Immun 80:3993–4003. Nettleship JE, editors. Functional and structural proteomics of Shi X, Huang Y, Mao Y, Naimy H, Zaia J. 2012c. Tandem mass spectrometry glycoproteins. Dordrecht: Springer. pp. 103–125. of heparan sulfate negative ions: Sulfate loss patterns and chemical Singh SK, Streng-Ouwehand I, Litjens M, Kalay H, Burgdorf S, Saeland E, modification methods for improvement of product ion profiles. J Am Kurts C, Unger WW, van Kooyk Y. 2011c. Design of neo-glycoconju- Soc Mass Spectrom 23:1498–1511. gates that target the mannose receptor and enhance TLR- independent Shibata TK, Matsumura F, Wang P, Yu S, Chou C-C, Khoo K-H, Kitayama cross-presentation and Th1 polarization. Eur J Immunol 41:916–925. K, Akama TO, Sugihara K, Kanayama N, Kojima-Aikawa K, Singh SK, SaiSree L, Amrutha RN, Reddy M. 2012. Three redundant murein Seeberger PH, Fukuda M, Suzuki A, Aoki D, Fukuda MN. 2012. endopeptidases catalyse an essential cleavage step in peptidoglycan Identification of mono- and disulfated N-acetyl-lactosaminyl oligosac- synthesis of Escherichia coli K12. Mol Microbiol 86:1036–1051. charide structures as epitopes specifically recognized by humanized Sipos A, Tor€ ok€ Z, Roth€ E, Kiss-Szikszai A, Batta G, Bereczki I, Fejes Z, monoclonal antibody HMOCC-1 raised against ovarian cancer. J Biol Borbas A, Ostorhazi E, Rozgonyi F, Naesens L, Herczegh P. 2012. Chem 287:6592–6602. Synthesis of isoindole and benzoisoindole derivatives of teicoplanin Shimizu H, Iwayama Y, Imamura A, Ando H, Ishida H, Kiso M. 2011. pseudoaglycon with remarkable antibacterial and antiviral activities. Synthesis of the disialic acid-embedded glycan part of ganglioside Bioorg Med Chem Lett 22:7092–7096. HPG-1. Biosci Biotechnol Biochem 75:2079–2082. Sisti F, Fernandez J, Higgins SC, Casabuono A, Couto A, Mills KHG, Shimma S, Kubo A, Satoh T, Toyoda M. 2012. Detailed structural analysis of Hozbor D. 2011. A deep rough type structure in Bordetella bronchisep- lipids directly on tissue specimens using a MALDI-spiralTOF- tica lipopolysaccharide modulates host immune responses. Microbiol reflectron TOF mass spectrometer. PLoS One 7:e37107. Immunol 55:847–854. Shimura Y, Suzuki J, Kasuya MCZ, Matsuoka K, Hatanaka K. 2012a. A Sisu E, Flangea C, Serb A, Zamfir AD. 2011. Modern developments in mass novel method for the production of glycosphingolipids. Helv Chim spectrometry of chondroitin and dermatan sulfate glycosaminoglycans. Acta 95:67–75. Amino Acids 41:235–256. Shimura Y, Suzuki J, Muraoka M, Carmelita M, Kasuya Z, Matsuoka K, Skhirtladze A, Perrone A, Montoro P, Benidze M, Kemertelidze E, Pizza C, Hatanaka K. 2012b. Large scale biosynthesis of ganglioside analogues Piacente S. 2011. Steroidal saponins from Yucca gloriosa L. rhizomes: by RERF-LC-A1 cells cultured in HYPERFlask. Prep Biochem LC-MS profiling, isolation and quantitative determination. Phytochem- Biotechnol 42:378–392. istry 72:126–135. Shinchi H, Wakao M, Nakagawa S, Mochizuki E, Kuwabata S, Suda Y. Slamti L, de Pedro MA, Guichet E, Picardeau M. 2011. Deciphering 2012. Stable sugar-chain-immobilized fluorescent nanoparticles for morphological determinants of the helix-shaped leptospira. J Bacteriol probing lectin and cells. Chem Asian J 7:2678–2682. 193:6266–6275. Shu X, Liang M, Yang B, Li Y, Liu C, Wang Y, Shu J. 2012. Lipid Slosarczyk AT, Baltzer L. 2012. Efficient formation of heterodimers from fingerprinting of Bacillus spp. using online MALDI-TOF mass peptides and proteins using unsymmetrical polyfluorophenyl esters of spectrometry. Anal Meth 4:3111–3117. dicarboxylic acids. J Peptide Sci 18:261–269. Shuo T, Koshikawa N, Hoshino D, Minegishi T, Ao-Kondo H, Oyama M, Slosarczyk AT, Ramapanicker R, Norberg T, Baltzer L. 2012. Mixed Sekiya S, Iwamoto S, Tanaka K, Seiki M. 2012. Detection of the pentafluorophenyl and o-fluorophenyl esters of aliphatic dicarboxylic heterogeneous O-glycosylation profile of MT1-MMP expressed in acids: Efficient tools for peptide and protein conjugation. RSC Adv cancer cells by a simple MALDI-MS method. PLoS One 7:e43751. 2:908–914. Si C-L, Zhang Y, Zhu Z-Y, Liu S-C. 2011. Chemical constituents with Smet-Nocca C, Broncel M, Wieruszeski J-M, Tokarski C, Hanoulle X, Leroy antioxidant activity from the pericarps of Juglans sigillata. Chem Nat A, Landrieu I, Rolando C, Lippens G, Hackenberger CPR. 2011. Compds 47:442–445. Identification of O-GlcNAc sites within peptides of the Tau protein and Silchenko AS, Kalinovsky AI, Avilov SA, Andryjashchenko PV, Dmitrenok their impact on phosphorylation. Mol Biosyst 7:1420–1429. PS, Kalinin VI, Stonik VA. 2012. 3b-O-Glycosylated 16b-acetoxy-9b- Sobhany M, Kakuta Y, Sugiura N, Kimata K, Negishi M. 2012. The H-lanosta-7,24-diene-3b,18,20b-triol, an intermediate metabolite structural basis for a coordinated reaction catalyzed by a bifunctional

158 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

glycosyltransferase in chondroitin biosynthesis. J Biol Chem adamantyl end-functionalized polymers. Macromolecules 44:3250– 287:36022–36028. 3259. Sokolova RV, Ermakova SP, Awada SM, Zvyagintseva TN, Kanaan HM. Stancanelli R, Løjkner LD, Larsen KL, Guardo M, Cannava C, Tommasini 2011. Composition, structural characteristics and antitumor properties S, Ventura CA, Calabro ML, Micali N, Villari V, Mazzaglia A. 2012. of polysaccharides from the brown algae Dictyopteris polypodioides Structural and spectroscopic features of lutein/butanoyl-b-cyclodextrin and Sargassum sp. Chem Nat Compds 47:329–334. nanoassemblies. J Pharm Biomed Anal 71:214–218. Song J, Abe K, Imanaka H, Imamura K, Minoda M, Yamaguchi S, Nakanishi Stansell E, Canis K, Haslam SM, Dell A, Desrosiers RC. 2011. Simian K. 2011a. Causes of the production of multiple forms of b-galactosi- immunodeficiency virus from the sooty mangabey and rhesus macaque dase by Bacillus circulans. Biosci Biotechnol Biochem 75:268–278. is modified with O-linked carbohydrate. J Virol 85:582–595. Song W, Henquet MGL, Mentink RA, van Dijk AJ, Cordewener JHG, Bosch Staples GO, Zaia J. 2011. Analysis of glycosaminoglycans using mass D, America AHP, van der Krol AR. 2011b. N-Glycoproteomics in spectrometry. Curr Proteomics 8:325–336. plants: Perspectives and challenges. J Proteomics 74:1463–1474. Staples GO, Zaia J. 2011. Mass spectrometry in carbohydrate sequencing Song X, Heimburg-Molinaro J, Smith DF, Cummings RD. 2011c. Derivati- and binding. In: Wang B, Boons G-J, editors. Carbohydrate recogni- zation of free natural glycans for incorporation onto glycan arrays: tion: Biological problems, methods, and applications. Hoboken: John Derivatizing glycans on the microscale for microarray and other Wiley and Sons. pp. 257–300. applications. Curr Protoc Chem Biol 3:53–63. Staubach S, Schadewaldt P, Wendel U, Nohroudi K, Hanisch F-G. 2012. Song X, Lasanajak Y, Xia B, Heimburg-Molinaro J, Rhea JM, Ju H, Zhao C, Differential glycomics of epithelial membrane glycoproteins from Molinaro RJ, Cummings RD, Smith DF. 2011d. Shotgun glycomics: A urinary exovesicles reveals shifts toward complex-type N-glycosyla- microarray strategy for functional glycomics. Nat Meth 8:85–90. tion in classical galactosemia. J Proteome Res 11:906–916. Song X, Yu H, Chen X, Lasanajak Y, Tappert MM, Air GM, Tiwari VK, Cao Steenackers A, Cazet A, Bobowski M, Rombouts Y, Lefebvre J, Guerardel Y, H, Chokhawala HA, Zheng H, Cummings RD, Smith DF. 2011e. A Tulasne D, Bourhis XL, Delannoy P. 2012a. Expression of GD3 sialylated glycan microarray reveals novel interactions of modified synthase modifies ganglioside profile and increases migration of MCF- sialic acids with proteins and viruses. J Biol Chem 286:31610–31622. 7 breast cancer cells. C R Chemie 15:3–14. Song Y-R, Song N-E, Kim J-H, Nho Y-C, Baik S-H. 2011f. Exopolysacchar- Steenackers A, Vanbeselaere J, Cazet A, Bobowski M, Rombouts Y, Colomb ide produced by Bacillus licheniformis strains isolated from Kimchi. J F, Le Bourhis X, Guerardel Y, Delannoy P. 2012b. Accumulation of Gen Appl Microbiol 57:169–175. unusual gangliosides GQ3 and GP3 in breast cancer cells expressing Song X, Smith DF, Cummings RD. 2012a. Nonenzymatic release of free the GD3 synthase. Molecules 17:9559–9572. reducing glycans from glycosphingolipids. Anal Biochem 429:82–87. Stefanowicz-Hajduk J, Kawiak A, Gajdus J, Ochocka JR, Paszkiewicz M, Song X, Heimburg-Molinaro J, Dahms NM, Smith DF, Cummings RD. Stepnowski P, Łojkowska E. 2011. Cytotoxic activity of Paris 2012b. Preparation of a mannose-6-phosphate glycan microarray quadrifolia extract and isolated saponin fractions against human tumor through fluorescent derivatization, phosphorylation, and immobiliza- cell lines. Acta Biol Cracov Bot 53:127–131. tion of natural high-mannose N-glycans and application in ligand Stepan H, Pabst M, Altmann F, Geyer H, Geyer R, Staudacher E. 2012. O- identification of P-type lectins. Methods Mol Biol 808:137–148. Glycosylation of snails. Glycoconj J 29:189–198. Souady J, Hulsewig€ M, Distler U, Haier J, Denz A, Pilarsky C, Senninger N, Stepper J, Shastri S, Loo TS, Preston JC, Novak P, Man P, Moore CH, Dreisewerd K, Peter-KatalinicJ,Muthing€ J. 2011. Differences in Havlcek V, Patchett ML, Norris GE. 2011. Cysteine S-glycosylation, a CD75s- and iso-CD75s-ganglioside content and altered mRNA expres- new post-translational modification found in glycopeptide bacterio- sion of sialyltransferases ST6GAL1 and ST3GAL6 in human hepato- cins. FEBS Lett 585:645–650. cellular carcinomas and nontumoral liver tissues. Glycobiology Stovbun SV, Berlin AA, Mikhailov AI, Sergienko VI, Govorun VM, Demina 21:584–594. IA, Kalinina TS. 2012. Physicochemical properties of high-molecular- Spadiut O, Ibatullin FM, Peart J, Gullfot F, Martinez-Fleites C, Ruda M, Xu weight plant polysaccharide of hexose glycoside class (Panavir) with C, Sundqvist G, Davies GJ, Brumer H. 2011. Building custom antiviral activity. Nanotechnol Russ 7:539–543. polysaccharides in vitro with an efficient, broad-specificity xyloglucan Stringano E, Cramer R, Hayes W, Smith C, Gibson T, Mueller-Harvey I. glycosynthase and a fucosyltransferase. J Am Chem Soc 133:10892– 2011. Deciphering the complexity of sainfoin (Onobrychis viciifolia) 10900. proanthocyanidins by MALDI-TOF mass spectrometry with a judi- Spearman M, Dionne B, Butler M. 2011. The role of glycosylation in cious choice of isotope patterns and matrixes. Anal Chem 83:4147– therapeutic antibodies. In: Al-Rubeai M, editor. Antibody expression 4153. and production, cell engineering 7. Dordrecht Heidelberg, London, Struwe WB, Reinhold VN. 2012. The conserved oligomeric Golgi complex New York: Springer. pp. 251–292. is required for fucosylation of N-glycans in Caenorhabditis elegans. Srinivas P, Kollapalli SP, Thomas A. 2012. Bioactive hyaluronan fragment Glycobiology 22:863–875. (hexasaccharide) detects specific hexa-binding proteins in human Struwe WB, Cosgrave EFJ, Byrne JC, Saldova R, Rudd PM. 2011. breast and stomach cancer: Possible role in tumorogenesis. Indian J Glycoproteomics in health and disease. In: Owens RJ, Nettleship JE, Biochem Biophys 49:228–235. editors. Functional and structural proteomics of glycoproteins. Dor- Sriwilaijaroen N, Kondo S, Yagi H, Takemae N, Saito T, Hiramatsu H, Kato drecht: Springer. pp. 1–38. K, Yasuo S. 2011. N-Glycans from porcine trachea and lung: Sturiale L, Barone R, Garozzo D. 2011a. The impact of mass spectrometry in Predominant NeuAca2-6Gal could be a selective pressure for influenza the diagnosis of congenital disorders of glycosylation. J Inherit Metab variants in favor of human-type receptor. PLoS One 6:e16302. Dis 34:891–899. Sriwilaijaroen N, Kondo S, Yagi H, Hiramatsu H, Nakakita S-i Yamada K, Sturiale L, Palmigiano A, Silipo A, Knirel YA, Anisimov AP, Lanzetta R, Ito H, Hirabayashi J, Narimatsu H, Kato K, Suzuki Y. 2012. Bovine Parrilli M, Molinaro A, Garozzo D. 2011b. Reflectron MALDI TOF milk whey for preparation of natural N-glycans: Structural and and MALDI TOF/TOF mass spectrometry reveal novel structural quantitative analysis. Open Glycosci 5:41–50. details of native lipooligosaccharides. J Mass Spectrom 46:1135–1142. St. Michael F, Cairns C, Filion AL, Neelamegan D, Lacelle S, Cox AD. Styslinger TJ, Zhang N, Bhatt VS, Pettit N, Palmer AF, Wang PG. 2012. 2011. Investigating the candidacy of lipopolysaccharide-based glyco- Site-selective glycosylation of hemoglobin with variable molecular conjugates as vaccines to combat Mannheimia haemolytica. Glycoconj weight oligosaccharides: Potential alternative to PEGylation. J Am J 28:397–410. Chem Soc 134:7507–7515. Stadermann J, Komber H, Erber M, D€abritz F, Ritter H, Voit B. 2011. Suchanowska A, Kaczmarek R, Duk M, Lukasiewicz J, Smolarek D, Diblock copolymer formation via self-assembly of cyclodextrin and Majorczyk E, Jaskiewicz E, Laskowska A, Wasniowska K, Grodecka

Mass Spectrometry Reviews DOI 10.1002/mas 159 & HARVEY

M, Lisowska E, Czerwinski M. 2012. A single point mutation in the Suzuki A, Miyazaki M, Matsuda J, Yoneshige A. 2011a. High-performance gene encoding Gb3/CD77 synthase causes a rare inherited polyaggluti- thin-layer chromatography/mass spectrometry for the analysis of nation syndrome. J Biol Chem 287:38220–38230. neutral glycosphingolipids. Biochim Biophys Acta 1811:861–874. Suda Y, Okazaki F, Hasegawa Y, Adachi S, Fukase K, Kokubo S, Kuramitsu Suzuki N, Nawa D, Yamamoto K. 2011b. Distinct expression profiles of S, Kusumoto S. 2012. Structural characterization of neutral and acidic UDP-galactose: b-D-galactoside a1,4-galactosyltransferase and UDP- glycolipids from Thermus thermophilus HB8. PLoS One 7:e35067. galactose: b-D-galactoside b1,4-galactosyltransferase in pigeon, os- Sugiura Y, Setou M. 2010. Matrix-assisted laser desorption/ionization and trich and chicken. Glycobiology 21:283–294. nanoparticle-based imaging mass spectrometry for small metabolites: Suzuki T, Maeda T, Nomura S, Suzuki M, Grant G, Sporns P. 2011c. Rapid A practical protocol. Methods Mol Biol 656:173–195. analysis of fructans and comparison of fructan profiles in several Sugiura N, Setoyama Y, Chiba M, Kimata K, Watanabe H. 2011. Baculovirus different types of asparagus storage roots using MALDI-TOF MS. J envelope protein ODV-E66 is a novel chondroitinase with distinct Hortic Sci Biotech 86:210–216. substrate specificity. J Biol Chem 286:29026–29034. Suzuki J, Fujino T. 2012. Matrix-assisted laser desorption ionization mass Sugiura N, Shioiri T, Chiba M, Sato T, Narimatsu H, Kimata K, Watanabe H. spectrometry of maltohexaose and acetylsalicylic acid using alkali 2012. Construction of a chondroitin sulfate library with defined metal cation-substituted zeolites. Anal Sci 28:901–904. structures and analysis of molecular interactions. J Biol Chem Suzuki Y, Kabayama K. 2012. Convenient and rapid removal of detergent 287:43390–43400. from glycolipids in detergent-resistant membrane microdomains. J Suila H, Pitk€anen V, Hirvonen T, Heiskanen A, Anderson H, Laitinen A, Lipid Res 53:599–608. Natunen S, Miller-Podraza H, Satomaa T, Natunen J, Laitinen S, Valmu Svensson J, Bergman A-C, Adamson U, Blomb€ack M, Wallen H, Jorneskog€ L. 2011. Are globoseries glycosphingolipids SSEA-3 and -4 markers G. 2012. Acetylation and glycation of fibrinogen in vitro occur at for stem cells derived from human umbilical cord blood? J Mol Cell specific lysine residues in a concentration dependent manner: A mass Biol 99–107. spectrometric and isotope labeling study. Biochem Biophys Res Sullards MC, Liu Y, Chen Y, Merrill AHJ. 2011. Analysis of mammalian Commun 421:335–342. sphingolipids by liquid chromatography tandem mass spectrometry Svoboda M, Mann BF, Goetz JA, Novotny MV. 2012. Examination of glycan (LC-MS/MS) and tissue imaging mass spectrometry (TIMS). Biochim profiles from IgG-depleted human immunoglobulins facilitated by Biophys Acta 1811:838–853. microscale affinity chromatography. Anal Chem 84:3269–3277. Sumer-Bayraktar Z, Kolarich D, Campbell MP, Ali S, Packer NH, Thaysen- Swarts BM, Guo Z. 2011. Chemical synthesis and functionalization of Andersen M. 2011. N-Glycans modulate the function of clickable glycosylphosphatidylinositol anchors. Chem Sci 2:2342– human corticosteroid-binding globulin. Mol Cell Proteomics 10: 2352. M111.009100. Swierzko A, Lukasiewicz J, Cedzynski M, Maciejewska A, Jachymek W, Sumer-Bayraktar Z, Nguyen-Khuong T, Jayo R, Chen DDY, Ali S, Packer Niedziela T, Matsushita M, Lugowski C. 2012. New functional ligands NH, Thaysen-Andersen M. 2012. Micro- and macroheterogeneity of for ficolin-3 among lipopolysaccharides of Hafnia alvei. Glycobiology N-glycosylation yields size and charge isoforms of human sex hormone 22:267–280. binding globulin circulating in serum. Proteomics 12:3315–3327. Syson K, Stevenson CEM, Rejzek M, Fairhurst SA, Nair A, Bruton CJ, Field Sumiyoshi W, Nakakita SI, Miyanishi N, Yamada K, Hasehira K, Nakakita RA, Chater KF, Lawson DM, Bornemann S. 2011. Structure of Y, Hirabayashi J. 2012. Hypersialylated type-I lactosamine-containing Streptomyces maltosyltransferase GlgE, a homologue of a genetically N-glycans found in Artiodactyla sera are potential xenoantigens. validated anti-tuberculosis target. J Biol Chem 286:38298–38310. Glycobiology 22:1031–1041. Tagliabracci VS, Heiss C, Karthik C, Contreras CJ, Glushka J, Ishihara M, Sun W, Six D, Kuang X, Roland KL, Raetz CRH, Curtiss R, III. 2011a. A Azadi P, Hurley TD, DePaoli-Roach AA, Roach PJ. 2011. Phosphate live attenuated strain of Yersinia pestis KIM as a vaccine against incorporation during glycogen synthesis and Lafora disease. Cell plague. Vaccine 29:2986–2998. Metab 13:274–282. ̊ Sun W, Grassi P, Engstrom€ A, Sooriyaarachchi S, Ubhayasekera W, Tajiri M, Wada Y. 2011. Infrared matrix-assisted laser desorption/ionization Hreinsson J, Wa˚nggren K, Clark GF, Dell A, Schedin-Weiss S. 2011b. mass spectrometry for quantification of glycosaminoglycans and N-glycans of human protein C inhibitor: Tissue-specific expression and gangliosides. Int J Mass Spectrom 305:164–169. function. PLoS One 6:e29011. Takahashi D, Hirono S, Toshima K. 2011a. Target-selective photodegrada- Sun Y, Zhang J, Li C, Guan H, Yu G. 2012a. Synthesis of glycoglycerolipid tion of oligosaccharides by a fullerene-boronic acid hybrid upon visible of 1,2-dipalmitoyl-3-(N-palmitoyl-6’-amino-6’- deoxy-a-D-glucosyl)- light irradiation. Chem Commun 47:11712–11714. sn-glycerol and its analogues, inhibitors of human Myt1-kinase. Takahashi M, Morita T, Wada K, Hirose N, Fukuoka T, Imura T, Kitamoto D. Carbohydr Res 355:6–12. 2011b. Production of sophorolipid glycolipid biosurfactants from Sun Y, Senger K, Baginski TK, Mazloom A, Chinn Y, Pantua H, Hamidzadeh sugarcane molasses using Starmerella bombicola NBRC 10243. J Oleo K, Ramani SR, Luis E, Tom I, Sebrell A, Quinones G, Ma Y, Mukhyala Sci 60:267–273. K, Sai T, Ding J, Haley B, Shadnia H, Kapadia SB, Gonzalez LC, Hass PE, Zarrin AA. 2012b. Evolutionarily conserved paired immunoglobu- Takahashi H, Yanagisawa T, Kim KS, Yokoyama S, Ohnishia M. 2012. lin-like receptor a (PILRa) domain mediates its interaction with Meningococcal PilV potentiates Neisseria meningitidis type IV pilus- diverse sialylated ligands. J Biol Chem 287:15837–15850. mediated internalization into human endothelial and epithelial cells. Infect Immun 80:4154–4166. Sun Z, Findsen EW, Isailovic D. 2012. Atmospheric pressure visible- wavelength MALDI-MS. Int J Mass Spectrom 315:66–73. Takahashi D, Toshima K. 2012a. Chemistry based approach for degradation of target-oligosaccharides using photo-activatable organic small mole- Sundaram S, Matathia A, Qian J, Zhang J, Hsieh M-C, Liu T, Crowley R, cules. Trends Glycosci Glycotechnol 24:258–276. Parekh B, Zhou Q. 2011. An innovative approach for the characterization of the isoforms of a monoclonal antibody product. mAbs 3:505– Takahashi D, Toshima K. 2012b. Chemical methods for degradation of target 512. oligosaccharides using designed light-activatable organic molecules. Chem Commun 48:4397–4407. Sundekilde UK, Barile D, Meyrand M, Poulsen NA, Larsen LB, Lebrilla CB, German JB, Bertram HC. 2012. Natural variability in bovine milk Takashima Y, Yuting Y, Otsubo M, Yamaguchi H, Harada A. 2012. oligosaccharides from Danish Jersey and Holstein-Friesian breeds. J Supramolecular hydrogels formed from poly(viologen) cross-linked Agric Food Chem 60:6188–6196. with cyclodextrin dimers and their physical properties. Beilstein J Org Chem 8:1594–1600. Sureshkumar G, Hotha S. 2012. AuBr3 mediated glycosidations: Synthesis of tetrasaccharide motif of the Leishmania donovani lipophosphogly- Takeda N, Ikeda-Matsumi R, Ebara-Nagahara K, Otaki-Nanjo M, Taniguchi- can. Glycoconj J 29:221–230. Morita K, Nanjo M, Tamura J-I. 2012. Synthesis of heparan sulfate

160 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

tetrasaccharide as a substrate for human heparanase. Carbohydr Res Thomas Al, Charbonneau JL, Fournaise E, Chaurand P. 2012. Sublimation of 353:13–21. new matrix candidates for high spatial resolution imaging mass Taki T. 2012. An approach to glycobiology from glycolipidomics: Ganglio- spectrometry of lipids: Enhanced information in both positive and side molecular scanning in the brains of patients with Alzheimer’s negative polarities after 1,5-diaminonapthalene deposition. Anal Chem disease by TLC-blot/matrix assisted laser desorption/ionization-time 84:2048–2054. of flight MS. Biol Pharm Bull 35:1642–1647. Thompson AJ, Williams RJ, Hakki Z, Alonzi DS, Wennekes T, Gloster TM, Takimori S, Shimaoka H, Furukawa J-I, Yamashita T, Amano M, Fujitani N, Songsrirote K, Thomas-Oates JE, Wrodnigg TM, Spreitz J, Stutz€ AE, Takegawa Y, Hammarstrom€ L, Kacskovics I, Shinohara Y, Nishimura Butters TD, Williams SJ, Davies GJ. 2012. Structural and mechanistic S-I. 2011. Alteration of the N-glycome of bovine milk glycoproteins insight into N-glycan processing by endo-a-mannosidase. Proc Natl during early lactation. FEBS J 278:3769–3781. Acad Sci USA 109:781–786. Talat S, Thiruvikraman M, Kumari S, Kaur KJ. 2011. Glycosylated analogs Thuy TT, Ingan€as M, Ekstrand G, Thorsen G. 2010. Parallel sample of formaecin I and drosocin exhibit differential pattern of antibacterial preparation of proteins, from crude samples to crystals ready for activity. Glycoconj J 28:537–555. MALDI-MS, in an integrated microfluidic system. J Chromatogr B Tan H, Xue Y, Luan Q, Yao X. 2012. Evaluation of glycol chitosan-graft- 878:2803–2810. carboxymethyl b-cyclodextrin as potential pH-sensitive anticancer Thuy TT, Ingan€as M, Thorsen G. 2011. High-throughput profiling of N- drug carrier by surface plasmon resonance. Anal Meth 4:2784–2790. linked oligosaccharides in therapeutic antibodies using a microfluidic CD platform and MALDI-MS. Anal Bioanal Chem 399:1601–1611. Tanaka K, Yamada M, Tamiya-Koizumi K, Kannagi R, Aoyama T, ̊ Hara A, Kyogashima M. 2011. Systematic analyses of free Thuy TT, Tengstrand E, Aberg M, Thorsen G. 2012. Discrimination between ceramide species and ceramide species comprising neutral glycosphin- glycosylation patterns of therapeutic antibodies using a microfluidic golipids by MALDI-TOF MS with high- energy CID. Glycoconj J platform, MALDI-MS and multivariate statistics. J Pharm Biomed 28:67–87. Anal 70:47–52. Tanaka H, Yoshimura Y, Dovichi NJ, Palcic MM, Hindsgaul O. 2012. A Tian X, Pai J, Baek K-H, Ko S-K, Shin I. 2011. Fluorophore-labeled, concise chemical synthesis of a fluorescent bGal-(1,4)-S-bGlc-Cer peptide-based glycoclusters: Synthesis, binding properties for lectins, derivative and its enzymatic elongation by glycosyltransferases. and detection of carbohydrate-binding proteins in cells. Chem Asian J Tetrahedron Lett 53:1812–1815. 6:2107–2113. Tao N, Wu S, Kim J, An HJ, Hinde K, Power ML, Gagneux P, German JB, Tian X, Pai J, Shin I. 2012. Analysis of density-dependent binding of glycans Lebrilla CB. 2011. Evolutionary glycomics: Characterization of milk by lectins using carbohydrate microarrays. Chem Asian J 7:2052– oligosaccharides in primates. J Proteome Res 10:1548–1557. 2060. Temuujin U, Chi W-J, Lee S-Y, Chang Y-K, Hong S-K. 2011. Tishchenko G, Simůnek J, Brus J, Netopilk M, Pekarek M, WalterovaZ, Overexpression and biochemical characterization of DagA from Koppova I, Lenfeld J. 2011. Low-molecular-weight chitosans: Prepara- Streptomyces coelicolor A3(2): An endo-type b-agarase producing tion and characterization. Carbohydr Polym 86:1077–1081. neoagarotetraose and neoagarohexaose. Appl Microbiol Biotechnol Tissandie E, Morelle W, Berthelot L, Vrtovsnik F, Daugas E, Walker F, 92:749–759. Lebrec D, Trawale J-M, Francoz C, Durand F, Moura IC, Paradis V, Temuujin U, Chi W-J, Chang Y-K, Hong S-K. 2012. Identification and Moreau R, Monteiro RC. 2011. Both IgA nephropathy and alcoholic biochemical characterization of Sco3487 from Streptomyces coelicolor cirrhosis feature abnormally glycosylated IgA1 and soluble CD89-IgA A3(2), an exo- and endo-type b-agarase-producing neoagarobiose. J and IgG-IgA complexes: Common mechanisms for distinct diseases. Bacteriol 194:142–149. Kidney Int 80:1352–1363. Tep S, Hincapie M, Hancock WS. 2012a. A MALDI-TOF MS method for Tomabechi Y, Inazu T. 2011. Preparation of pseudo glycoamino acid and its the simultaneous and quantitative analysis of neutral and sialylated application to glycopeptide synthesis. Tetrahedron Lett 52:6504–6507. glycans of CHO-expressed glycoproteins. Carbohydr Res 347:121– Tong W, Han H, Song Z, Ma C, Pan Y, Zhang Y, Qin W, Qian X. 2012. 129. Chemical derivatization with a polycyclic aromatic hydrocarbon for Tep S, Hincapie M, Hancock WS. 2012b. The characterization and highly sensitive detection of N-linked glycans using MALDI-TOF MS. quantitation of glycomic changes in CHO cells during a bioreactor Anal Meth 4:3531–3535. campaign. Biotechnol Bioeng 109:3007–3117. Torrelles JB, Sieling PA, Arcos J, Knaup R, Bartling C, Rajaram MVS, Stenger S, Modlin RL, Schlesinger LS. 2011. Structural differences in Tep S, Hincapie M, Hancock WS. 2012c. A general approach for the lipomannans from pathogenic and nonpathogenic mycobacteria that purification and quantitative glycomic analysis of human plasma. Anal impact CD1b-restricted T cell responses. J Biol Chem 286:35438– Bioanal Chem 402:2687–2700. 35446. Terao J. 2011. P-conjugated molecules covered by permethylated cyclo- Tothiam C, Phrompittayarat W, Putalun W, Tanaka H, Sakamoto S, Khane dextrins. Chem Record 11:269–283. IA, Ingkaninan K. 2011. An enzyme-linked immunosorbant assay Terao J, Ikai K, Kambe N, Seki S, Saeki A, Ohkoshi K, Fujihara T, Tsuji Y. using monoclonal antibody against bacoside A3 for determination of 2011. Synthesis of a head-to-tail-type cyclodextrin-based insulated jujubogenin glycosides in Bacopa monnieri (L.) Wettst. Phytochem molecular wire. Chem Commun 47:6816–6818. Anal 22:385–391. Testova L, Chong S-L, Tenkanen M, Sixta H. 2011. Autohydrolysis of birch Touboul D, Brunelle A, Laprevote O. 2011. Mass spectrometry imaging: wood. Holzforschung 65:535–542. Towards a lipid microscope? Biochemie 93:113–119. Teuber K, Schiller J, Jakop U, Lupold€ S, Orledge JM, Blount JD, Royle NJ, Toukach PV. 2011. Bacterial carbohydrate structure database 3: Principles Hoodless A, Muller€ K. 2011. MALDI-TOF mass spectrometry as a and realization. J Chem Inf Model 51:159–170. simple tool to determine the phospholipid/glycolipid composition of sperm: Pheasant spermatozoa as one selected example. Anim Reprod Tousi F, Hancock WS, Hincapie M. 2011. Technologies and strategies for Sci 123:270–278. glycoproteomics and glycomics and their application to clinical Thadke SA, Kar M, Gupta SS, Hotha S. 2011. Gold catalyzed glycosidations biomarker research. Anal Meth 3:20–32. for the synthesis of sugar acrylate/acrylamide hybrids and their utility. Toyama A, Nakagawa H, Matsuda K, Ishikawa N, Kohno N, Daigo Y, Sato Carbohydr Res 346:1511–1518. T-A, Nakamura Y, Ueda K. 2011. Deglycosylation and label-free Thaysen-Andersen M, Wilkinson BL, Payne RJ, Packer NH. 2011. Site- quantitative LC-MALDI MS applied to efficient serum biomarker specific characterisation of densely O-glycosylated mucin-type pep- discovery of lung cancer. Proteome Sci 9: Article 18. tides using electron transfer dissociation ESI-MS/MS. Electrophoresis Tran DN, Blaszkiewicz C, Menuel S, Roucoux A, Philippot K, Hapiot F, 32:3536–3545. Monflier E. 2011. Using click chemistry to access mono- and ditopic

Mass Spectrometry Reviews DOI 10.1002/mas 161 & HARVEY

b-cyclodextrin hosts substituted by chiral amino acids. Carbohydr Res Urban PL, Amantonico A, Zenobi R. 2011. Lab-on-a-plate: Extending the 346:210–218. functionality of MALDI-MS and LDI-MS targets. Mass Spectrom Rev Tran DT, Lim J-M, Liu M, Stalnaker SH, Wells L, Ten Hagen KG, Live D. 30:435–478. 2012a. Glycosylation of a-dystroglycan. O-Mannosylation influences Urbanowicz BR, Pena~ MJ, Ratnaparkhe S, Avci U, Backe J, Steet HF, the subsequent addition of GalNAc by UDP-GalNAc polypeptide N- Foston M, Li H, O’Neill MA, Ragauskas AJ, Darvill AG, Wyman C, acetylgalactosaminyltransferes. J Biol Chem 287:20967–20974. Gilbert HJ, York WS. 2012. 4-O-methylation of glucuronic acid in Tran TH, Park S, Lee H, Park S, Kim B, Kim O-H, Oh B-C, Lee D, Arabidopsis glucuronoxylan is catalyzed by a domain of unknown Lee H. 2012b. Ultrasmall gold nanoparticles for highly specific function family 579 protein. Proc Natl Acad Sci USA 109:14253– isolation/enrichment of N-linked glycosylated peptides. Analyst 137: 14258. 991–998. Urita A, Matsuhashi T, Onodera T, Nakagawa H, Hato M, Amano M, Seito Trastoy B, Bonsor DA, Perez-Ojeda ME, Jimeno ML, Mendez-Ardoy A, N, Minami A, Nishimura S-I, Iwasaki N. 2011. Alterations of high- Fernandez JMG, Sundberg EJ, Chiara JL. 2012. Synthesis and mannose type N-glycosylation in human and mouse osteoarthritis biophysical study of disassembling nano hybrid bioconjugates with a cartilage. Arthritis Rheum 63:3428–3438. cubic octasilsesquioxane core. Adv Funct Mater 22:3191–3201. Usov AI. 2011. Polysaccharides of the red algae. Adv Carbohydr Chem Triguero A, Cabrera G, Rodrguez M, Soto J, Zamora Y, Perez M, Wormald Biochem 65:115–217. MR, Cremata JA. 2011. Differential N-glycosylation of a monoclonal Valderrama-Rincon JD, Fisher AC, Merritt JH, Fan Y-Y, Reading CA, antibody expressed in tobacco leaves with and without endoplasmic Chhiba K, Heiss C, Azadi P, Aebi M, DeLisa MP. 2012. An engineered reticulum retention signal apparently induces similar in vivo stability in eukaryotic protein glycosylation pathway in Escherichia coli. Nat mice. Plant Biotechnol J 9:1120–1130. Chem Biol 8:434–436. Trimpin S, Wang B, Inutan ED, Li J, Lietz CB, Harron A, Pagnotti VS, Valdes-Gonzalez T, Goto-Inoue N, Hayasaka T, Ishiyama H, Setou M, Taki Sardelis D, McEwen CN. 2012. A mechanism for ionization of T. 2011a. Imaging technology of complex lipid molecular species by a nonvolatile compounds in mass spectrometry: Considerations from combination of TLC-blot and MALDI-TOF—special reference to MALDI and inlet ionization. J Am Soc Mass Spectrom 23:1644–1660. human brain ganglioside molecular species. J Glycom Lipidom 1: Tryfona T, Liang H-C, Kotake T, Tsumuraya Y, Stephens E, Dupree P. 2012. Article 1000104. Structural characterization of Arabidopsis leaf arabinogalactan poly- Valdes-Gonzalez T, Goto-Inoue N, Hirano W, Ishiyama H, Hayasaka T, saccharides. Plant Physiol 160:653–666. Setou M, Taki T. 2011b. New approach for glyco- and lipidomics— Tsai H-Y, Boonyapranai K, Sriyam S, Yu C-J, Wu S-W, Khoo K-H, Molecular scanning of human brain gangliosides by TLC-Blot and Phutrakul S, Chen S-T. 2011. Glycoproteomics analysis to identify a MALDI-QIT-TOF MS. J Neurochem 116:678–683. glycoform on haptoglobin associated with lung cancer. Proteomics Valenzuela SV, Diaz P, Pastor FIJ. 2012. Modular glucuronoxylan-specific 11:2162–2170. xylanase with a family CBM35 carbohydrate-binding module. Appl Tsai I-H, Chang H-C, Chen J-M, Cheng A-C, Khoo KH. 2012. Glycan Environ Microbiol 78:3923–3931. structures and intrageneric variations of venom acidic phospholipases van Bueren JJL, Rispens T, Verploegen S, van der Palen-Merkus T, Stapel S, A2 from Tropidolaemus pitvipers. FEBS J 279:2672–2682. Workman LJ, James H, van Berkel PHC, van de Winkel JGJ, Platts- Tsao C-W, DeVoe DL. 2011. Nanofilament silicon for matrix-free laser Mills TAE, Parren PWHI. 2011. Anti-galactose-a-1,3-galactose IgE desorption/ionization mass spectrometry. Methods Mol Biol 790:183– from allergic patients does not bind a-galactosylated glycans on intact 189. therapeutic antibody Fc domains. Nat Biotechnol 29:574–576. Tsubokawa D, Goso Y, Kawashima R, Ota H, Nakamura T, Nakamura K, van de Geijn FE, de Man YA, Wuhrer M, Willemsen SP, Deelder AM, Hazes Sato N, Kurihara M, Dohi T, Kawamura YI, Ichikawa T, Ishihara JMW, Dolhain RJEM. 2011. Mannose-binding lectin does not explain K. 2012. The monoclonal antibody HCM31 specifically recognises the course and outcome of pregnancy in rheumatoid arthritis. Arthritis the Sda tetrasaccharide in goblet cell mucin. FEBS Open Bio 2:223– Res Ther 13:R10. 233. van der Woude AD, Sarkar D, Bhatt A, Sparrius M, Raadsen SA, Boon L, Tutu E, Vigh G. 2011. Synthesis, analytical characterization and Geurtsen J, van der Sar AM, Luirink J, Houben ENG, Besra GS, Bitter initial capillary electrophoretic use in an acidic background electrolyte W. 2012. Unexpected link between lipooligosaccharide biosynthesis of a new, single-isomer chiral resolving agent: Heptakis(2-O-sulfo-3- and surface protein release in Mycobacterium marinum. J Biol Chem O-methyl-6-O-acetyl)-b-cyclodextrin. Electrophoresis 32:2655–2662. 287:20417–20429. Tuzimski T. 2011. Application of different modes of thin-layer chromatogra- Van Dongen FEM, Van Eylen D, Kabel MA. 2011. Characterization of phy and mass spectrometry for the separation and detection of large substituents in xylans from corn cobs and stover. Carbohydr Polym and small biomolecules. J Chromatogr A 1218:8799–8812. 86:722–731. UcaktS urk€ E. 2012. Analysis of glycoforms on the glycosylation site and the Van Dyck S, Caulier G, Todesco M, Gerbaux P, Fournier I, Wisztorski M, glycans in monoclonal antibody biopharmaceuticals. J Sep Sci 35:341– Flammang P. 2011. The triterpene glycosides of Holothuria forskali: 350. Usefulness and efficiency as a chemical defense mechanism against Uchinashi Y, Nagasaki M, Zhou J, Tanaka K, Fukase K. 2011. Reinvestiga- predatory fish. J Exp Biol 214:1347–1356. tion of the C5-acetamide sialic acid donor for a-selective sialylation: Van Gool MP, Vancso I, Schols HA, Toth K, Szakacs G, Gruppen H. 2011. practical procedure under microfluidic conditions. Org Biomol Chem Screening for distinct xylan degrading enzymes in complex shake flask 9:7243–7248. fermentation supernatants. Bioresource Technol 102:6039–6047. Umegatani Y, Izawa H, Nawaji M, Yamamoto K, Kubo A, Yanase M, Takaha van Kampen JJA, Burgers PC, de Groot R, Gruters RA, Luider TM. 2011. T, Kadokawa J-I. 2012. Enzymatic a-glucuronylation of maltooligo- Biomedical application of MALDI mass spectrometry for small- saccharides using a-glucuronic acid 1-phosphate as glycosyl donor molecule analysis. Mass Spectrom Rev 30:101–120. catalyzed by a thermostable phosphorylase from Aquifex aeolicus VF5. van Leeuwen SS, Schoemaker RJW, Timmer CJAM, Kamerling JP, Carbohydr Res 350:81–85. Dijkhuizen L. 2012a. Use of Wisteria floribunda agglutinin affinity Unak G, Ozkaya F, Medine EI, Kozgus O, Sakarya S, Bekis R, Unak P, chromatography in the structural analysis of the bovine lactoferrin N- Timur S. 2012. Gold nanoparticle probes: Design and in vitro linked glycosylation. Biochim Biophys Acta 1820:1444–1455. applications in cancer cell culture. Colloid Surface B 90:217–226. van Leeuwen SS, Schoemaker RJW, Timmer CJAM, Kamerling JP, Unterieser I, Cuers J, Voiges K, Enebro J, Mischnick P. 2011. Quantitative Dijkhuizen L. 2012b. N- and O-glycosylation of a commercial bovine aspects in electrospray ionization ion trap and matrix-assisted laser whey protein product. J Agric Food Chem 60:12553–12564. desorption/ionization time-of-flight mass spectrometry of malto-oligo- van Munster JM, van der Kaaij RM, Dijkhuizen L, van der Maarel MJEC. saccharides. Rapid Commun Mass Spectrom 25:2201–2208. 2012. Biochemical characterization of Aspergillus niger CfcI, a

162 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

glycoside hydrolase family 18 chitinase that releases monomers during phase synthesis of hyaluronan oligosaccharides. Org Lett 14:3776– substrate hydrolysis. Microbiol Immunol 158:2168–2179. 3779. Vanbeselaere J, Chang L-Y, Harduin-Lepers A, Fabre E, Yamakawa N, Wang C. 2011. Synthesis of a glycodendrimer with five repeating mannoside Slomianny C, Biot C, Khoo K-H, Guerardel Y. 2012. Mapping the units. Adv Mater Res 284–286:1819–1822. expressed glycome and glycosyltransferases of zebrafish liver cells as a Wang H, van der Donk WA. 2011. Substrate selectivity of the sublancin relevant model system for glycosylation studies. J Proteome Res S-glycosyltransferase. J Am Chem Soc 133:16394–16397. 11:2164–2177. Wang W, Liu H, Li Z. 2011. Tandem mass spectrometric characterization of Vancova M, Sterba J, Dupejova J, Simonova Z, Nebesarova J, Novotny MV, fetuin sialylated glycopeptides enriched by TiO2 microcolumn. Chin J Grubhoffer L. 2012. Uptake and incorporation of sialic acid by the tick Chem 29:2229–2235. Ixodes ricinus . J Insect Physiol 58:1277–1287. Wang A, Li W, Zhang P, Ling C-C. 2011a. Synthesis of a novel class of Vasseur JA, Goetz JA, Alley WR, Jr., Novotny MV. 2012. Smoking and lung cyclodextrin-based nanotubes. Org Lett 13:3572–3575. N cancer-induced changes in -glycosylation of blood serum proteins. Wang C, Sanders B, Baker DC. 2011b. Synthesis of a glycodendrimer Glycobiology 22:1684–1708. incorporating multiple mannosides on a glucoside core. Canad J Chem Vats A, Singh AK, Mukherjee R, Chopra T, Ravindran MS, Mohanty D, 89:959–963. Chatterji D, Reyrat J-M, Gokhale RS. 2012. Retrobiosynthetic Wang C, Fan W, Zhang P, Wang Z, Huang L. 2011c. One-pot nonreductive approach delineates the biosynthetic pathway and the structure of O- glycan release and labeling with 1-phenyl-3-methyl-5-pyrazolone the acyl chain of mycobacterial glycopeptidolipids. J Biol Chem followed by ESI-MS analysis. Proteomics 11:4229–4242. 287:30677–30687. Wang G, Pu K-Y, Zhang X, Li K, Wang L, Cai L, Ding D, Lai Y-H, Liu B. Vazquez G, Santos J, Freire MS, Antorrena G, Gonzalez- Alvarez J. 2012. 2011d. Star-shaped glycosylated conjugated oligomer for two-photon Eucalyptus globulus Extraction of antioxidants from eucalyptus ( ) bark. fluorescence imaging of live cells. Chem Mater 23:4428–4434. Wood Sci Technol 46:443–457. Wang H-Y, Chu X, Zhao Z-X, He X-S, Guo Y-L. 2011e. Analysis of low Velasco-Torrijos T, Abbey L, O’Flaherty R. 2012. A concise synthesis of molecular weight compounds by MALDI-FTICR-MS. J Chromatogr B glycolipids based on aspartic acid building blocks. Molecules 879:1166–1179. 17:11346–11362. Wang H, Wang H, Zhang L, Zhang J, Leng J, Cai T, Guo Y. 2011f. Velkova L, Dolashka P, Lieb B, Dolashki A, Voelter W, Van Beeumen J, Improvement and extension of the application scope for matrix- Devreese B. 2011. Glycan structures of the structural subunit (HtH1) of assisted laser desorption/ionization mass spectrometric analysis-orient- Haliotis tuberculata hemocyanin. Glycoconj J 28:385–395. ed N-alkylpyridinium isotope quaternization. Anal Chim Acta Verma SC, Mahadevan S. 2012. The chbG gene of the chitobiose (chb) 707:100–106. operon of Escherichia coli encodes a chitooligosaccharide deacetylase. Wang H, Wong C-H, Chin A, Taguchi A, Taylor A, Hanash S, Sekiya S, J Bacteriol 194:4959–4971. Takahashi H, Murase M, Kajihara S, Iwamoto S, Tanaka K. 2011g. Vibert A, Jacquinet J-C, Lopin-Bon C. 2011. Recent advances in the Integrated mass spectrometry-based analysis of plasma glycoproteins chemical and enzymatic chondroitin sulfate synthesis. J Carbohydr and their glycan modifications. Nat Protocols 6:253–269. Chem 30:393–414. Wang J, Balog CIA, Stavenhagen K, Koeleman CAM, Scherer HU, Selman Vickerman JC. 2011. Molecular imaging and depth profiling by mass MHJ, Deelder AM, Huizinga TWJ, Toes REM, Wuhrer M. 2011h. Fc- spectrometry-SIMS, MALDI or DESI?. Analyst 136:2199–2217. Glycosylation of IgG1 is modulated by B-cell stimuli. Mol Cell Vidadala SR, Thadke SA, Hotha S, Kashyap S. 2012. Synthesis of thioglyco- Proteomics 10:M110.004655. sides from propargyl glycosides exploiting alkynophilic gold catalyst. Wang L, Kamijo Y, Matsumoto A, Nakajima T, Higuchi M, Kannagi R, J Carbohydr Chem 31:241–251. Kyogashima M, Aoyama T, Hara A. 2011i. Kidney transplantation Vieira AC, An HJ, Ozcan S, Kim J-H, Lebrilla CB, Mannis MJ. 2012. recovers the reduction level of serum sulfatide in ESRD patients via Glycomic analysis of tear and saliva in ocular rosacea patients: The processes correlated to oxidative stress and platelet count. Glycoconj J search for a biomarker. Ocul Surf 10:184–192. 28:125–135. Visvanathan M, Siddam SR, Lee I-H, Lushington GH, Bousfield GR. 2011. Wang Q, Shi X, Leymarie N, Madico G, Sharon J, Costello CE, Zaia J. GlycomicsDB—A data integration platform for glycans and their 2011j. A typical preparation of Francisella tularensis O-antigen yields strucutres. Open Med Inform J 5:9–16. a mixture of three types of saccharides. Biochemistry (Moscow) 50:10941–10950. Vojtech M, Petrusova M, Valent I, Pribulova B, Petrus L. 2011. Preparation of D-galactofuranosyl nitromethanes: a revision and a new approach. Wang S-H, Wu S-W, Khoo K-H. 201k. MS-based glycomic strategies for Carbohydr Res 346:715–721. probing the structural details of polylactosaminoglycan chain on N- glycans and glycoproteomic identification of its protein carriers. von der Lieth C-W, Freire AA, Blank D, Campbell MP, Ceroni A, Damerell Proteomics 11:2812–2829. DR, Dell A, Dwek RA, Ernst B, Fogh R, Frank M, Geyer H, Geyer R, Harrison MJ, Henrick K, Herget S, Hull WE, Ionides J, Joshi HJ, Wang W, Hale C, Goulding D, Haslam SM, Tissot B, Lindsay C, Kamerling JP, Leeflang BR, Lutteke€ T, Lundborg M, Maass K, Merry Michell S, Titball R, Yu J, Toribio AL, Rossi R, Dell A, Bradley A, A, Ranzinger R, Rosen J, Royle L, Rudd PM, Schloissnig S, Stenutz R, Dougan G. 2011m. Mannosidase 2, alpha 1 deficiency is associated Vranken WF, Widmalm G, Haslam SM. 2011. EUROCarbDB: An with ricin resistance in embryonic stem (ES) cells. PLoS One 6: open-access platform for glycoinformatics. Glycobiology 21:493–502. e22993. Vorholter€ F-J, Wiggerich H-G, Scheidle H, Sidhu VK, Mrozek K, Kuster€ H, Wang Z, Takashima Y, Yamaguchi H, Harada A. 2011n. Photoresponsive Puhler€ A, Niehaus K. 2012. Involvement of bacterial TonB-dependent formation of pseudorotaxane with cyclodextrin derivatives. Org Lett signaling in the generation of an oligogalacturonide damage-associated 13:4356–4359. molecular pattern from plant cell walls exposed to Xanthomonas Wang C. 2012. Synthesis of a disaccharide with a mannose unit and a thiol campestris pv. campestris pectate lyases. BMC Microbiol 12: Article tether. Adv Mater Res 487:706–709. 239. Wang Q, Ismail B. 2012. Effect of Maillard-induced glycosylation on the Wada Y, Kadoya M, Okamoto N. 2012. Mass spectrometry of apolipoprotein nutritional quality, solubility, thermal stability and molecular configu- C-III, a simple analytical method for mucin-type O-glycosylation and ration of whey protein. Int Dairy J 25:112–122. its application to an autosomal recessive cutis laxa type-2 (ARCL2) Wang B, Chun J, Liu Y, Han L, Wang Y-S, Joo E-J, Kim Y-S, Cheng M-S. patient. Glycobiology 22:1140–1144. 2012a. Synthesis of novel diosgenyl saponin analogues and apoptosis- Walvoort MTC, Volbeda AG, Reintjens NRM, van den Elst H, Plante OJ, inducing activity on A549 human lung adenocarcinoma. Org Biomol Overkleeft HS, van der Marel GA, Codee JDC. 2012. Automated solid- Chem 10:8822–8834.

Mass Spectrometry Reviews DOI 10.1002/mas 163 & HARVEY

Wang G, Lo LF, Forsberg LS, Maier RJ. 2012b. Helicobacter pylori rene and glass slides and their analysis by MALDI-TOF MS. Beilstein peptidoglycan modifications confer lysozyme resistance and contribute J Org Chem 8:753–762. to survival in the host. mBio 3:e00409–e00412. Werneburg M, Zerbe K, Juhas M, Bigler L, Stalder U, Kaech A, Wang G, Zhang X, Geng J, Li K, Ding D, Pu K-Y, Cai L, Lai Y-H, Liu B. Ziegler U, Obrecht D, Eberl L, Robinson JA. 2012. Inhibition of 2012c. Glycosylated star-shaped conjugated oligomers for targeted lipopolysaccharide transport to the outer membrane in Pseudomonas two-photon fluorescence imaging. Chem Eur J 18:9705–9713. aeruginosa by peptidomimetic antibiotics. ChemBioChem 13:1767– Wang J, Rong W, Hu X, Liu X, Jiang L, Ma Y, Dang G, Liu Z, Wei F. 2012d. 1775. Hyaluronan tetrasaccharide in the cerebrospinal fluid is associated with Werner A, Horstkorte R, Glanz D, Biskup K, Blanchard V, Berger M, Bork self-repair of rats after chronic spinal cord compression. Neuroscience K. 2012. Glycoengineering the N-acyl side chain of sialic acid of 210:467–480. human erythropoietin affects its resistance to sialidase. Biol Chem Wang P-P, Yu G-L, Jiao G-L, Zhao X, Li J, Chai W-G. 2012e. Analysis of N- 393:777–783. glycans profiling from hela cells by matrix-assisted laser desorption/ Westereng B, Ishida T, Vaaje-Kolstad G, Wu M, Eijsink VGH, Igarashi K, ionization time-of-flight mass spectrometry. Chem J Chin Univ Samejima M, Sta˚hlberg J, Horn SJ, Sandgren M. 2011. The putative 33:1233–1238. endoglucanase PcGH61D from Phanerochaete chrysosporium is a Wang S-L, Liu C-P, Liang T-W. 2012f. Fermented and enzymatic production metal-dependent oxidative enzyme that cleaves cellulose. PLoS One 6: of chitin/chitosan oligosaccharides by extracellular chitinases from e27807. Bacillus cereus TKU027. Carbohydr Polym 90:1305–1313. Wheeler SF, Domann P, Harvey DJ. 2009. Derivatization of sialic acids for Wang S, Xie W, Zhang X, Zou X, Zhang Y. 2012g. Disulfide- and terminal stabilization in matrix-assisted laser desorption/ionization mass spec- alkyne- functionalized magnetic silica particles for enrichment of azido trometry and concomitant differentiation of a(2-3) and a (2-6) isomers. glycopeptides. Chem Commun 48:5907–5909. Rapid Commun Mass Spectrom 23:303–312. Wang X, Miao S, Wang P, Zhang S. 2012h. Highly efficient synthesis of Whitehead SN, Chan KHN, Gangaraju S, Slinn J, Li J, Hou ST. 2011. sucrose monolaurate by alkaline protease Protex 6L. Bioresource Imaging mass spectrometry detection of gangliosides species in the Technol 109:7–12. mouse brain following transient focal cerebral ischemia and long-term Wang Z-J, Chauvin B, Maillard P, Hammerer F, Carez D, Croisy A, Sandre recovery. PLoS One 6:e20808. C, Chollet-Martin S, Prognon P, Paul J-L, Blais J, Kasselouri A. 2012i. Whitman CM, Yang F, Kohler JJ. 2011. Modified GM3 gangliosides Glycodendrimeric phenylporphyrins as new candidates for retinoblas- produced by metabolic oligosaccharide engineering. Bioorg Med toma PDT: Blood carriers and photodynamic activity in cells. J Chem Lett 71:5006–5010. Photochem Photobiol B 115:16–24. Wichit S, Jittmittraphap A, Hidari KIPJ, Thaisomboonsuk B, Petmitr S, Ubol Ward S, Ling C-C. 2011. Efficient and versatile modification of the S, Aoki C, Itonori S, Morita K, Suzuki T, Suzuki Y, Jampangern W. secondary face of cyclodextrins through copper-catalyzed Huisgen 2011. Dengue virus type 2 recognizes the carbohydrate moiety of 1,3-dipolar cycloaddition. Eur J Org Chem 4853–4861. neutral glycosphingolipids in mammalian and mosquito cells. Micro- Weber C, Czaplewska JA, Baumgaertel A, Altuntas E, Gottschaldt M, biol Immunol 55:135–140. Hoogenboom R, Schubert US. 2012. A sugar decorated macromolecu- Wilkinson BL, Chun CKY, Payne RJ. 2011. Synthesis of MUC1 glycopeptide lar bottle brush by carbohydrate-initiated cationic ring-opening poly- thioesters and ligation via direct aminolysis. Peptide Sci 96:137–146. merization. Macromolecules 45:46–55. Wilkinson BL, Day S, Chapman R, Perrier S, Apostolopoulos V, Payne RJ. Wehner JW, Weissenborn MJ, Hartmann M, Gray CJ, Sardz k R, Eyers CE, 2012a. Synthesis and immunological evaluation of self-assembling and Flitsch SL, Lindhorst TK. 2012. Dual purpose S-trityl-linkers for self-adjuvanting tricomponent glycopeptide cancer-vaccine candi- glycoarray fabrication on both polystyrene and gold. Org Biomol dates. Chem Eur J 18:16540–16548. Chem 10:8919–8926. Wilkinson BL, Stone RS, Capicciotti CJ, Thaysen-Andersen M, Matthews Wei H, Zheng W, Diakur J, Wiebe LI. 2011. Confocal laser scanning JM, Packer NH, Ben RN, Payne RJ. 2012b. Total synthesis of microscopy (CLSM) based evidence for cell permeation by mono-4- homogeneous antifreeze glycopeptides and glycoproteins. Angew (N-6-deoxy-6-amino-b-cyclodextrin)-7- nitrobenzofuran (NBD-b- Chem Int Ed 51:3606–3610. CyD). Int J Pharm 403:15–22. Wilson IBH. 2012. The class I a1,2-mannosidases of Caenorhabditis Wei G, Wei D, Du Y. 2012. An alternative total synthesis of solamargine. Sci elegans. Glycoconj J 29:173–179. China Chem 55:1247–1251. Wisniewski JR, Zielinska DF, Mann M. 2011. Comparison of ultrafiltration Wei J, Shi L, Zhang X, Xu G, Chen C. 2012. Synthesis of calixarene-b- units for proteomic and N-glycoproteomic analysis by the filter-aided cyclodextrin Schiff base and adsorption of basic fuchsin on it. Shiyou sample preparation method. Anal Biochem 410:307–309. Huagong/. Petrochem Technol 41:1065–1070. Wojnar JM, Northcote PT. 2011. The agminosides: Naturally acetylated Wei W, Fu Y-j, Zu Y-G, Wang W, Luo M, Zhao C-J, Li C-Y, Zhang L, Wei Z- glycolipids from the New Zealand marine sponge Raspailia agminata. F. 2012. Ionic liquid-based microwave-assisted extraction for the J Nat Prods 74:69–73. determination of flavonoid glycosides in pigeon pea leaves by high Woo H-J, Kang H-K, Nguyen TTH, Kim G-E, Kim Y-M, Park J-S, Kim D, performance liquid chromatography-diode array detector with penta- Cha J, Moon Y-H, Nam S-H, Xia Y-m Kimura A, Kim D. 2012. fluorophenyl column. J Sep Sci 35:2875–2883. Synthesis and characterization of ampelopsin glucosides using dex- Weidmann S, Kemmerling S, M€adler S, Stahlberg H, Braun T, Zenobi R. transucrase from Leuconostoc mesenteroides B-1299CB4: Glucosyla- 2012. Ionic liquids as matrices in microfluidic sample deposition for tion enhancing physicochemical properties. Enzyme Microb Technol high-mass matrix-assisted laser desorption/ionization mass spectrome- 51:311–318. try. Eur J Mass Spectrom 18:279–286. Woodin CL, Hua D, Maxon M, Rebecchi KR, Go EP, Desaire H. 2012. Weignerova L, Marhol P, GerstorferovaD,Kren V. 2012. Preparatory GlycoPep Grader: A web-based utility for assigning the composition of production of quercetin-3-b-D-glucopyranoside using alkali-tolerant N-linked glycopeptides. Anal Chem 84:4821–4829. thermostable a-L-rhamnosidase from Aspergillus terreus. Bioresource Wormann€ ME, Corrigan RM, Simpson PJ, Matthews SJ, Grundling€ A. 2011. Technol 115:222–227. Enzymatic activities and functional interdependencies of Bacillus Weiss NG, Jarvis JW, Nelson RW, Hayes MA. 2011. Examining serum subtilis lipoteichoic acid synthesis enzymes. Mol Microbiol 79:566– amyloid P component microheterogeneity using capillary isoelectric 583. focusing and MALDI-MS. Proteomics 11:106–113. Wu S, Grimm R, German JB, Lebrilla CB. 2011. Annotation and structural Weissenborn MJ, Wehner JW, Gray CJ, Sardz k R, Eyers CE, Lindhorst TK, analysis of sialylated human milk oligosaccharides. J Proteome Res Flitsch SL. 2012. Formation of carbohydrate-functionalised polysty- 10:856–868.

164 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Wu H, Aam BB, Wang W, Norberg AL, Sørlie M, Eijsink VGH, Du Y. 2012. Yamada M, Yao I, Hayasaka T, Ushijima M, Matsuura M, Takada H, Shikata Inhibition of angiogenesis by chitooligosaccharides with specific N, Setou M, Kwon A-H, Ito S. 2012b. Identification of oligosacchar- degrees of acetylation and polymerization. Carbohydr Polym 89:511– ides from histopathological sections by MALDI imaging mass 518. spectrometry. Anal Bioanal Chem 402:1921–1930. Wuhrer M, Deelder AM, van der Burgt YEM. 2011. Mass spectrometric Yamakoshi Y, Yamakoshi F, Hu JC-C, Simmer JP. 2012. Characterization of glycan rearrangements. Mass Spectrom Rev 30:664–680. kallikrein-related peptidase 4 glycosylations. Eur J Oral Sci 119:234– Wunschel DS, Wahl KL, Melville AM, Sorensen CM, Colburn HA, 240. Valentine NB, Stamper CL. 2011. Determination of post-culture Yamano K, Koizumi A, Takeda T, Kiuchi F, Hada N. 2012. Gala1-4Galb1- processing with carbohydrates by MALDI-MS and TMS derivatization 3GalNAc is the dominant epitope of Em2 antigen, the mucin-type GC-MS. Talanta 85:2352–2360. glycoprotein from Echinococcus multilocularis. Parasitol Res 111: Xia L, Zheng RB, Lowary TL. 2012. Revisiting the specificity of an a- 795–805. (1!4)-mannosyltransferase involved in mycobacterial methylman- Yamauchi K, Saka S. 2010. Characterization of oligosaccharides with nose polysaccharide biosynthesis. ChemBioChem 13:1139–1151. MALDI-TOF/MS derived from Japanese beech cellulose as treated by Xin L, Zhang H, Liu H, Li Z. 2012. Equal ratio of graphite carbon to hot-compressed water. In: Yao T, editor. Zero-carbon energy Kyoto, activated charcoal for enrichment of N-glycopeptides prior to matrix- 2010. Japan: Springer. pp. 95–99. assisted laser desorption/ionization time-of-flight mass spectrometric Yameogo JBG, Geze A, Choisnard L, Putaux J-L, Gansane A, Sirima SB, identification. Rapid Commun Mass Spectrom 26:269–274. Semde R, Wouessidjewe D. 2012. Self-assembled biotransesterified Xiong Z, Zhao L, Wang F, Zhu J, Qin H, Wu Ra, Zhang W, Zou H. 2012. cyclodextrins as Artemisinin nanocarriers—I: Formulation, lyoavail- Synthesis of branched PEG brushes hybrid hydrophilic magnetic ability and in vitro antimalarial activity assessment. Eur J Pharm nanoparticles for the selective enrichment of N-linked glycopeptides. Biopharm 80:508–517. Chem Commun 48:8138–8140. Yan J, Li W, Liu K, Wu D, Chen F, Wu P, Zhang A. 2011. Thermoresponsive Xu P, Alam MM, Kalsy A, Charles RC, Calderwood SB, Qadri F, Ryan ET, supramolecular dendronized polymers. Chem Asian J 6:3260–3269. Kovac P. 2011a. Simple, direct conjugation of bacterial O-SP-core Yan S, Bleuler-Martinez S, Plaza DF, Kunzler€ M, Aebi M, Joachim A, antigens to proteins: Development of cholera conjugate vaccines. Razzazi-Fazeli E, Jantsch V, Geyer R, Wilson IBH, Paschinger K. Bioconjug Chem 22:2179–2185. 2012. Galactosylated fucose epitopes in nematodes. Increased expres- Xu Z, Lin C, Liao M. 2011b. Structure analysis of a new oligosaccharides sion in a Caenorhabditis mutant associated with altered lectin BROS from Blumea riparia. Chin J Org Chem 31:1811–1819. sensitivity and occurrence in parasitic species. J Biol Chem 287:28276–28290. Xu Z, Lin C, Shi Y. 2011c. Isolation and structure determination of a new oligosaccharide from Blume riparia. J Med Plant Res 5:2956– Yanaka S, Sano E, Naruse N, Miura K-i Futatsumori-Sugai M, Caaveiro 2962. JMM, Tsumoto K. 2011. Non-core region modulates interleukin-11 signaling activity: Generation of agonist and antagonist variants. J Biol Xu C, Spadiut O, Araffljo AC, Nakhai A, Brumer H. 2012a. Chemo- Chem 286:8085–8093. enzymatic assembly of clickable cellulose surfaces via multivalent polysaccharides. ChemSusChem 5:661–665. Yang B, Solakyildirim K, Chang Y, Linhardt RJ. 2011a. Hyphenated techniques for the analysis of heparin and heparan sulfate. Anal Xu G, Liu X, Liu QY, Zhou Y, Li J. 2012b. Improve accuracy and sensibility Bioanal Chem 399:541–557. in glycan structure prediction by matching glycan isotope abundance. Yang F, Lin Z, He X, Chen L, Zhang Y. 2011b. Synthesis and application of a Anal Chim Acta 743:80–89. macroporous boronate affinity monolithic column using a metal- Xue L, Ranjan N, Arya DP. 2011a. Synthesis and spectroscopic studies of the organic gel as a porogenic template for the specific capture of aminoglycoside (neomycin)-perylene conjugate binding to human glycoproteins. J Chromatogr A 1218:9194–9201. telomeric DNA. Biochemistry 50:2838–2849. Yang H, Yu Y, Song F, Liu S. 2011c. Structural characterization of neutral Xue Y-L, Miyakawa T, Hayashi Y, Okamoto K, Hu F, Mitani N, Furihata K, oligosaccharides by laser-enhanced in-source decay of MALDI-FTICR Sawano Y, Tanokura M. 2011b. Isolation and tyrosinase inhibitory MS. J Am Soc Mass Spectrom 22:845–855. effects of polyphenols from the leaves of persimmon, Diospyros kaki.J Yang H, Wang J, Song F, Zhou Y, Liu S. 2011d. Isoliquiritigenin (4,2’,4’- Agric Food Chem 59:6011–6017. trihydroxychalcone): A new matrix-assisted laser desorption/ioniza- Yagi H, Ohno E, Kondo S, Yoshida A, Kato K. 2011. Development and tion matrix with outstanding properties for the analysis of neutral application of multidimensional HPLC mapping method for O-linked oligosaccharides. Anal Chim Acta 701:45–51. oligosaccharides. Biomolecules 1:48–62. Yang X, Fu B, Yu B. 2011e. Total synthesis of landomycin A, a potent Yagi H, Saito T, Yanagisawa M, Yu RK, Kato K. 2012a. Lewis X-carrying antitumor angucycline antibiotic. J Am Chem Soc 133:12433–12435. N-glycans regulate the proliferation of mouse embryonic neural Yang Y, Liu T, Yang Y, Wu Q, Yang Q, Yu B. 2011f. Synthesis, evaluation, stem cells via the notch signaling pathway. J Biol Chem 287:24356– and mechanism of NNN-trimethyl-D-glucosamine-(1!4)-chitooligo- 24364. saccharides as selective inhibitors of glycosyl hydrolase family 20 b- Yagi H, Watanabe S, Suzuki T, Takahashi T, Suzuki Y, Kato K. 2012b. N-acetyl-D-hexosaminidases. ChemBioChem 12:457–467. Comparative analyses of N-glycosylation profiles of influenza A Yang W-B. 2012. Tandem mass spectrometry of tagged and permethylated viruses grown in different host cells. Open Glycosci 5:2–12. polysaccharides. In: Prasain J, editor. Mass spectrometry—Applica- YalcınS FN, Piacente S, Perrone A, Capasso A, Duman H, CalısS I._ 2012. tions and principles. Rijeka, Croatia: Intech. pp. 285–306. Cycloartane glycosides from Astragalus stereocalyx Bornm. Phyto- Yang S, Zhang H. 2012a. Solid-phase glycan isolation for glycomics chem Lett 73:119–126. analysis. Proteomics Clin Appl 6:596–608. Yamada K, Kakehi K. 2011. Recent advances in the analysis of carbohy- Yang SJ, Zhang H. 2012b. Glycan analysis by reversible reaction to drates for biomedical use. J Pharm Biomed Anal 55:702–727. hydrazide beads and mass spectrometry. Anal Chem 84:2232–2238. Yamada M, Someya CI, Nakahodo T, Maeda Y, Tsuchiya T, Akasaka T. Yang B, Yoshida K, Yin Z, Dai H, Kavunja H, El-Dakdouki MH, Sungsuwan 2011. Synthesis of endohedral metallofullerene glycoconjugates by S, Dulaney SB, Huang X. 2012a. Chemical synthesis of a heparan carbene addition. Molecules 16:9495–9504. sulfate glycopeptide: Syndecan-1. Angew Chem Int Ed 51:10185– Yamada K, Mitsui Y, Kakoi N, Kinoshita M, Hayakawa T, Kakehi K. 10189. 2012a. One-pot characterization of cancer cells by the analysis of Yang F, Chen Q, Cheng Q-Y, Yan C-G, Han B-H. 2012b. Sugar- mucin-type glycans and glycosaminoglycans. Anal Biochem 421:595– functionalized water-soluble cyclotriveratrylene derivatives: Prepara- 606. tion and interaction with fullerene. J Org Chem 77:971–976.

Mass Spectrometry Reviews DOI 10.1002/mas 165 & HARVEY

Yang H, Li M, Li Z, Liu S. 2012c. Gas-phase fragmentation of oligosacchar- Yu J, Sun J, Yu B. 2012a. Construction of interglycosidic N-O linkage via ides in MALDI laser-enhanced in-source decay induced by thermal direct glycosylation of sugar oximes. Org Lett 14:4022–4025. hydrogen radicals. Analyst 137:3624–1626. Yu M, Brown D, Reed C, Chung S, Lutman J, Stefanich E, Wong A, Stephan Yang X, Tao S, Orlando R, Brockhausen I, Kan FWK. 2012d. Structures and J-P, Bayer R. 2012b. Production, characterization, and pharmacokinet- biosynthesis of the N- and O-glycans of recombinant human oviduct- ic properties of antibodies with N-linked mannose-5 glycans. mAbs specific glycoprotein expressed in human embryonic kidney cells. 4:475–487. Carbohydr Res 358:47–55. Yu S-H, Wands AM, Kohler JJ. 2012c. Photoaffinity probes for studying Yavuz E, Maffioli C, Ilg K, Aebi M, Priem B. 2011. Glycomimicry: Display carbohydrate biology. J Carbohydr Chem 31:325–352. of fucosylation on the lipo-oligosaccharide of recombinant Escherichia Yu S-H, Boyce M, Wands AM, Bond MR, Bertozzi CR, Kohler JJ. 2012d. coli K12. Glycoconj J 28:39–47. Metabolic labeling enables selective photocrosslinking of O-GlcNAc- Ye J, Ly J, Watts K, Hsu A, Walker A, McLaughlin K, Berdichevsky M, modified proteins to their binding partners. Proc Natl Acad Sci USA Prinz B, Kersey DS, d’Anjou M, Pollard D, Potgieter T. 2011. 109:4834–4839. Optimization of a glycoengineered Pichia pastoris cultivation process Yu T, Xu X, Peng Y, Luo Y, Yang K. 2012e. Cell wall proteome of for commercial antibody production. Biotechnol Prog 27:1744–1750. Clostridium thermocellum and detection of glycoproteins. Microbiol Yin B-J, Gao T, Zheng N-Y, Li Y, Tang S-Y, Liang L-M, Xie Q. 2011. Res 167:364–371. Generation of glyco-engineered BY2 cell lines with decreased expres- Yu Y, Mishra S, Song X, Lasanajak Y, Bradley KC, Tappert MM, Air GM, sion of plant-specific glycoepitopes. Protein Cell 2:41–47. Steinhauer DA, Halder S, Cotmore S, Tattersall P, Agbandje-McKenna Yin Y-A, Qi J-C, Li W-H, Cao L-P, Wang Z-B. 2012a. Formation and M, Cummings RD, Smith DF. 2012f. Functional glycomic analysis of developmental characteristics of A- and B-type starch granules in human milk glycans reveals the presence of virus receptors and wheat endosperm. J Integrat Agric 11:73–81. embryonic stem cell biomarkers. J Biol Chem 287:44784–44799. Yin Z, Nguyen HG, Chowdhury S, Bentley P, Bruckman MA, Miermont A, Yuen C-T, Zhou Y, Wang Q-Z, Hou J-F, Bristow A, Wang J-Z. 2011. Glycan Gildersleeve JC, Wang Q, Huang X. 2012. Tobacco mosaic virus as a analysis of glycoprotein pharmaceuticals: Evaluation of analytical new carrier for tumor associated carbohydrate antigens. Bioconjug approaches to Z number determination in pharmaceutical erythropoie- Chem 23:1694–1703. tin products. Biologicals 39:396–403. Yokoyama M, Takegawa Y, Yamashita T. 2011. Establishment of an Yuki D, Sugiura Y, Zaima N, Akatsu H, Hashizume Y, Yamamoto T, analytical method for sialyl glycoprotein extraction from the experi- Fujiwara M, Sugiyama K, Setou M. 2011. Hydroxylated and non- mental hormone-induced estrous cycle of the mouse ovary. J Glycom hydroxylated sulfatide are distinctly distributed in the human cerebral Lipidom S4: Article 001. cortex. Neuroscience 193:44–53. Yoshida N, Tanaka T, Noguchi M, Kobayashi A, Ishikura K, Ikenuma T, Zabotina OA, Avci U, Cavalier D, Pattathil S, Chou Y-H, Eberhard S, Danhof Seno H, Watanabe T, Kohri M, Shoda S-I. 2012. One-pot chemo- L, Keegstra K, Hahn MG. 2012. Mutations in multiple XXT genes of enzymatic route to chitoheptaose via specific transglycosylation of Arabidopsis reveal the complexity of xyloglucan biosynthesis. Plant chitopentaose oxazoline on chitinase-template. Chem Lett 41:689– Physiol 159:1367–1384. 690. Zaccheus MV, Broeker NK, Lundborg M, Uetrecht C, Barbirz S, Widmalm Yoshimura Y, Zaima N, Moriyama T, Kawamura Y. 2012a. Different G. 2012. Structural studies of the O-antigen polysaccharide from localization patterns of anthocyanin species in the pericarp of black Escherichia coli TD2158 having O18 serogroup specificity and aspects rice revealed by imaging mass spectrometry. PLoS One 7:e31285. of its interaction with the tailspike endoglycosidase of the infecting Yoshimura Y, Enomoto H, Moriyama T, Kawamura Y, Setou M, Zaima N. bacteriophage HK620. Carbohydr Res 357:118–125. 2012b. Visualization of anthocyanin species in rabbiteye blueberry Zaidel DNA, Arnous A, Holck J, Meyer AS. 2011. Kinetics of enzyme- Vaccinium ashei by matrix-assisted laser desorption/ionization imag- catalyzed cross-linking of feruloylated arabinan from sugar beet. J ing mass spectrometry. Anal Bioanal Chem 403:1885–1895. Agric Food Chem 59:11598–11607. Yoshimura Y, Nudelman AS, Levery SB, Wandall HH, Bennett EP, Zakariassen H, Hansen MC, Jøranli M, Eijsink VGH, Sørlie M. 2011. Hindsgaul O, Clausen H, Nishimura S-I. 2012c. Elucidation of the Mutational effects on transglycosylating activity of family 18 chiti- sugar recognition ability of the lectin domain of UDP-GalNAc: nases and construction of a hypertransglycosylating mutant. Biochem- polypeptide N-acetylgalactosaminyltransferase 3 by using unnatural istry 50:5693–5703. glycopeptide substrates. Glycobiology 22:429–438. Zakharenko AM, Kusaykin MI, Kovalchuk SN, Anastyuk SD, Ly BM, Sova Yu L, Li X, Guo Z, Zhang X, Liang X. 2009. Hydrophilic interaction VV, Rasskazov VA, Zvyagintseva TN. 2011. Enzymatic and molecular chromatography based enrichment of glycopeptides by using click characterization of an endo-1,3-b-D-glucanase from the crystalline maltose: A matrix with high selectivity and glycosylation heterogene- styles of the mussel Perna viridis. Carbohydr Res 346:243–252. ity coverage. Chem Eur J 15:12618–12626. Zakharenko AM, Kusaykin MI, Kovalchuk SN, Sova VV, Silchenko AS, Yu C, Crispin M, Sonnen AF-P, Harvey DJ, Chang VT, Evans EJ, Scanlan Belik AA, Anastyuk SD, Ly BM, Rasskazov VA, Zvyagintseva TN. a CN, Stuart DI, Gilbert RJC, Davis SJ. 2011a. Use of the -mannosidase 2012. Catalytic properties and amino acid sequence of endo-1!3-b-D- I inhibitor kifunensine allows the crystallization of apo CTLA-4 glucanase from the marine mollusk Tapes literata. Biochemistry homodimer produced in long-term cultures of Chinese hamster ovary (Moscow) 77:878–888. cells. Acta Cryst F F67:785–789. Zaric SS, Coulter WA, Shelburne CE, Fulton CR, Zaric MS, Scott A, Lappin Yu S, Wang Q, Zhang J, Wu Q, Guo Z. 2011b. Synthesis and evaluation of MJ, Fitzgerald DC, Irwin CR, Taggart CC. 2011. Altered toll-like protein conjugates of GM3 derivatives carrying modified sialic acids as receptor 2-mediated endotoxin tolerance is related to diminished highly immunogenic cancer vaccine candidates. Med Chem Commun interferon b production. J Biol Chem 286:29492–29500. 2:524–530. Zauner G, Deelder AM, Wuhrer M. 2011. Recent advances in hydrophilic Yu T, Luo Y, Yang K. 2011c. Rapid characterization of N-linked glycosyla- interaction liquid chromatography (HILIC) for structural glycomics. tion site using non-specific protease digestion of gel-separated Electrophoresis 32:3456–3466. glycoproteins and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. Eur J Mass Spectrom 17:573–579. Zauner G, Kozak RP, Gardner RA, Fernandes DL, Deelder AM, Wuhrer M. Yu T, Guo C, Wang J, Hao P, Sui S, Chen X, Zhang R, Wang P, Yu G, Zhang 2012. Protein O-glycosylation analysis. Biol Chem 393:687–708. L, Dai Y, Li N. 2011d. Comprehensive characterization of the site- Zemkova Z, Garajova S, FlodrovaD,Rehulka P, Zelko I, VadkertiovaR, specific N-glycosylation of wild-type and recombinant human lactofer- Farkas V, Stratilova E. 2012. Incorporation of b-(1,6)-linked glucooli- rin expressed in the milk of transgenic cloned cattle. Glycobiology gosaccharides (pustulooligosaccharides) into plant cell wall structures. 21:206–224. Chem Papers 66:814–820.

166 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES &

Zemski Berry KA, Hankin JA, Barkley RM, Spraggins JM, Caprioli RM, Zhang M-Q, Liu Y, Xie S-X, Xu T-H, Liu T-H, Xu Y-J, Xu D-M. 2012c. A Murphy RC. 2011. MALDI imaging of lipid biochemistry in tissues by new triterpenoid saponin from Gymnema sylvestre. J Asian Nat Prod mass spectrometry. Chem Rev 111:6491–6512. Res 14:1186–1190. Zengerle M, Brandhuber F, Schneider C, Worek F, Reiter G, Kubik S. 2011. Zhang P, Haryadi R, Chan KF, Teo G, Goh J, Pereira NA, Feng H, Song Z. Highly efficient cyclosarin degradation mediated by a b-cyclodextrin 2012d. Identification of functional elements of the GDP-fucose derivative containing an oxime-derived substituent. Beilstein J Org transporter SLC35C1 using a novel Chinese hamster ovary mutant. Chem 7:1543–1554. Glycobiology 22:897–911. Zhang J, Ma PX. 2011. Core-shell structured nanoassemblies based on Zhang Q, Li G-Z, Becer CR, Haddleton DM. 2012e. Cyclodextrin-centred b-cyclodextrin containing block copolymer and poly(b-benzyl star polymers synthesized via a combination of thiol-ene click and ring L-aspartate) via host-guest complexation. Polymer 52:4928–4937. opening polymerization. Chem Commun 48:8063–8065. Zhang B, Sheng Q, Li X, Liang Q, Yan J, Liang X. 2011a. Selective Zhang S-J, Song X-Q, Yu B-S, Zhang B-C, Sun C-Q, Knox P, Zhou Y-H. enrichment of glycopeptides for mass spectrometry analysis using C18 2012f. Identification of quantitative trait loci affecting hemicellulose fractionation and titanium dioxide chromatography. J Sep Sci characteristics based on cell wall composition in a wild and cultivated 34:2745–2750. rice species. Mol Plant 5:162–175. Zhang H, Yao G, Deng C, Lu H, Yang P. 2011b. Facile synthesis of boronic Zhang X, He X, Chen L, Zhang Y. 2012g. Boronic acid modified magnetic acid-functionalized magnetic mesoporous silica nanocomposites for nanoparticles for enrichment of glycoproteins via azide and alkyne highly specific enrichment of glycopeptides. Chin J Chem 29:835–839. click chemistry. J Mater Chem 22:16520–16526. Zhang J, Siika-aho M, Tenkanen M, Viikari L. 2011c. The role of acetyl Zhang Y-M, Yang Z-X, Chen Y, Ding F, Liu Y. 2012h. Molecular binding xylan esterase in the solubilization of xylan and enzymatic hydrolysis and assembly behavior of b-cyclodextrin with piperazine and 1,4- of wheat straw and giant reed. Biotechnol Biofuels 4: Article 60. dioxane in aqueous solution and solid state. Cryst Growth Design Zhang J, Angala SK, Pramanik PK, Li K, Crick DC, Liav A, Jozwiak A, 12:1370–1377. Swiezewska E, Jackson M, Chatterjee D. 2011d. Reconstitution of Zhang Y, Yin H, Lu H. 2012i. Recent progress in quantitative glycoproteo- functional mycobacterial arabinosyltransferase AftC proteoliposome mics. Glycoconj J 29:249–258. and assessment of decaprenylphosphorylarabinose analogues as arabi- Zhang Y, Sinaiko AR, Nelsestuen GL. 2012j. Glycoproteins and glycosyla- nofuranosyl donors. ACS Chem Biol 6:819–828. tion: Apolipoprotein c3 glycoforms by top-down maldi-tof mass Zhang P, Zhang Y, Xue X, Wang C, Wang Z, Huang L. 2011e. Relative spectrometry. Methods Mol Biol 909:141–150. quantitation of glycans using stable isotopic labels 1-(d0/d5) phenyl-3- Zhang Y, Muthana SM, Barchi JJ, Jr., Gildersleeve JC. 2012k. Divergent methyl-5-pyrazolone by mass spectrometry. Anal Biochem 418:1–9. behavior of glycosylated threonine and serine derivatives in solid phase Zhang S, Shu H, Luo K, Kang X, Zhang Y, Lu H, Liu Y. 2011f. N-linked peptide synthesis. Org Lett 14:3958–3961. glycan changes of serum haptoglobin b chain in liver disease patients. Zhang Y, Muthana SM, Farnsworth D, Ludek O, Adams K, Barchi JJJ, Mol Biosyst 7:1621–1628. Gildersleeve JC. 2012l. Enhanced epimerization of glycosylated amino Zhang W-B, Li Y, Li X, Dong X, Yu X, Wang C-L, Wesdemiotis C, Quirk acids during solid-phase peptide synthesis. J Am Chem Soc 134:6316– RP, Cheng SZD. 2011g. Synthesis of shape amphiphiles based on 6325. functional polyhedral oligomeric silsesquioxane end-capped poly(L- Zhang Z, Zhao Y, Jiang L, Miao X, Zhou H, Jia L. 2012m. Glycomic lactide) with diverse head surface chemistry. Macromolecules alterations are associated with multidrug resistance in human leukemia. 44:2589–2596. Int J Biochem Cell Biol 44:1244–1253. Zhang W, Wang H, Tang H, Yang P. 2011h. Endoglycosidase-mediated Zhao Y, Yu L, Guo Z, Li X, Liang X. 2011. Reversed-phase depletion incorporation of 18O into glycans for relative glycan quantitation. Anal coupled with hydrophilic affinity enrichment for the selective isolation Chem 83:4975–4981. of N-linked glycopeptides by using Click OEG-CD matrix. Anal Zhang W, Wang H, Zhang L, Yao J, Yang P. 2011i. Large-scale assignment Bioanal Chem 399:3359–3365. of N-glycosylation sites using complementary enzymatic deglycosylation. Talanta 85:499–505. Zhao J, Schols HA, Chen Z, Jin Z, Buwalda P, Gruppen H. 2012a. Substituent distribution within cross-linked and hydroxypropylated Zhang X, Teng Y, Fu Y, Zhang S, Wang T, Wang C, Jin L, Zhang W. 2011j. sweet potato starch and potato starch. Food Chem 133:1333–1340. Lectin-based electrochemical biosensor constructed by functionalized carbon nanotubes for the competitive assay of glycan expression on Zhao X-L, Ma Y-Z, Wang K-Z. 2012b. Synthesis, pH-induced on-off-on living cancer cells. Chem Sci 2:2353–2360. luminescence switching, and partially intercalative DNA-binding and DNA photocleavage properties of an b-D-allopyranoside-grafted Zhang Y, Wang Z, Zhang X, Zhou W, Huang L. 2011k. One-pot fluorescent ruthenium(II) complex. J Inorg Biochem 113:66–76. labeling of saccharides with fluorescein-5-thiosemicarbazide for imaging polysaccharides transported in living cells. Carbohydr Res Zheng J-S, Xi W-X, Wang F-L, Li J, Guo Q-X. 2011a. Fmoc-SPPS chemistry 346:2156–2164. compatible approach for the generation of (glyco) peptide aryl thioesters. Tetrahedron Lett 52:2655–2660. Zhang Y, Giboulot A, Zivy M, Valot B, Jamet E, Albenne C. 2011l. Combining various strategies to increase the coverage of the plant cell Zheng Y, Hashidzume A, Takashima Y, Yamaguchi H, Harada A. 2011b. wall glycoproteome. Phytochemistry 72:1109–1123. Macroscopic observations of molecular recognition: Discrimination of the substituted position on the naphthyl group by polyacrylamide gel Zhang Y, Thomas TP, Lee K-H, Li M, Zong H, Desai AM, Kotlyar A, Huang modified with b-cyclodextrin. Langmuir 27:13790–13795. B, Holl MMB, Baker JRJ. 2011m. Polyvalent saccharide-functionalized generation 3 poly(amidoamine) dendrimer-methotrexate conju- Zhou W, Ha˚kansson K. 2011. Structural characterization of carbohydrates gate as a potential anticancer agent. Bioorg Med Chem 19:2557–2564. by Fourier transform tandem mass spectrometry. Curr Proteomics 8:297–308. Zhang Y, Gildersleeve JC. 2012. General procedure for the synthesis of neoglycoproteins and immobilization on epoxide-modified glass Zhou M, Thorson JS. 2011. Asymmetric enzymatic glycosylation of slides. Methods Mol Biol 808:155–165. mitoxantrone. Org Lett 13:2786–2788. Zhang H, Wang Z, Stupak J, Ghribi O, Geiger JD, Liu QY, Li J. 2012a. Zhou Q, Stefano JE, Harrahy J, Finn P, Avila L, Kyazike J, Wei R, Van Patten Targeted glycomics by selected reaction monitoring for highly sensi- SM, Gotschall R, Zheng X, Zhu Y, Edmunds T, Pan CQ. 2011. tive glycan compositional analysis. Proteomics 12:2510–2522. Strategies for neoglycan conjugation to human acid a-glucosidase. Zhang H, Yan Q, Kang Y, Zhou L, Zhou H, Yuan J, Wu S. 2012b. Fabrication Bioconjug Chem 22:741–751. of thermo-responsive hydrogels from star-shaped copolymer with a Zhou H, Briscoe AC, Froehlich JW, Lee RS. 2012a. PNGase F catalyzes de- biocompatible b-cyclodextrin core. Polymer 53:3719–3725. N-glycosylation in a domestic microwave. Anal Biochem 427:33–35.

Mass Spectrometry Reviews DOI 10.1002/mas 167 & HARVEY

Zhou P, Hu R, Chandan V, KuoLee R, Liu X, Chen W, Liu B, Altman E, Li J. Zhu XF, Shi YZ, Lei GJ, Fry SC, Zhang BC, Zhou YH, Braam J, Jiang T, Xu 2012b. Simultaneous analysis of cardiolipin and lipid A from XY, Mao CZ, Pan YJ, Yang JL, Wu P, Zheng SJ. 2012c. XTH31, Helicobacter pylori by matrix-assisted laser desorption/ionization encoding an in vitro XEH/XET-active enzyme, regulates aluminum time-of-flight mass spectrometry. Mol Biosyst 8:720–725. sensitivity by modulating in vivo XET action, cell wall xyloglucan Zhou Y, Marinescu L, Pedersen CM, Bols M. 2012c. Synthesis of tin- content, and aluminum binding capacity in Arabidopsis. Plant Cell containing cyclodextrins as potential enzyme models. Eur J Org Chem 24:4731–4747. 6383–6389. Zou G, Ochiai H, Huang W, Yang Q, Li C, Wang L-X. 2011. Chemo- Zhou Y, Lindb€ack E, Marinescu LG, Pedersen CM, Mikael B. 2012d. enzymatic synthesis and Fcg receptor binding of homogeneous glyco- Synthesis of cyclodextrins with carboxylic acids at the secondary rim forms of antibody Fc domain. Presence of a bisecting sugar moiety and an evaluation of their properties as chemzymes for glycoside enhances the affinity of Fc to FcgIIIa receptor. J Am Chem Soc hydrolysis. Eur J Org Chem 4063–4070. 166:18975–18991. Zhu X, Dere RT, Jiang J, Zhang L, Wang X. 2011. Synthesis of a-glycosyl Zou X, Liu D, Zhong L, Yang B, Lou Y, Yin Y. 2012. Synthesis and thiols by stereospecific ring-opening of 1,6-anhydrosugars. J Org characterization of a novel boronic acid-functionalized chitosan Chem 76:10187–10197. polymeric nanosphere for highly specific enrichment of glycopeptides. Carbohydr Polym 90:799–804. Zhu J, Wang F, Chen R, Cheng K, Xu B, Guo Z, Liang X, Ye M, Zou H. 2012a. Centrifugation assisted microreactor enables Zuberbuhler€ K, Casi G, Bernardes GJL, Neri D. 2012. Fucose-specific facile integration of trypsin digestion, hydrophilic interaction conjugation of hydrazide derivatives to a vascular-targeting monoclo- chromatography enrichment, and on-column deglycosylation for nal antibody in IgG format. Chem Commun 48:7100–7102. rapid and sensitive N-glycoproteome analysis. Anal Chem 84:5146– Zulueta MML, Lin S-Y, Lin Y-T, Huang C-J, Wang C-C, Ku C-C, Shi Z, Chyan 5153. C-L, Irene D, Lim L-H, Tsai T-I, Hu Y-P, Arco SD, Wong C-H, Hung Zhu X, Wu L, Mungra DC, Xia S, Zhu J. 2012b. Au@SiO2 core-shell S-C. 2012. a-Glycosylation by D-glucosamine-derived donors: Synthe- nanoparticles for laser desorption/ionization time of flight mass sis of heparosan and heparin analogues that interact with mycobacterial spectrometry. Analyst 137:2454–2458. heparin-binding hemagglutinin. J Am Chem Soc 124:8988–8995.

168 Mass Spectrometry Reviews DOI 10.1002/mas