An Update for the Period 2005–2006

ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES BY MATRIX-ASSISTED LASER DESORPTION/IONIZATION MASS SPECTROMETRY: AN UPDATE FOR THE PERIOD 2005–2006 David J. Harvey* Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, Oxford OX1 3QU, UK Received 01 December 2008; received (revised) 26 June 2009; accepted 13 July 2009 Published online 10 March 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mas.20265 This review is the fourth update of the original review, published (Mechref & Novotny, 2006), solid-phase tools such as micro- in 1999, on the application of MALDI mass spectrometry to the arrays (Larsen et al., 2006), capillary electrophoresis-MS analysis of carbohydrates and glycoconjugates and brings (Campa et al., 2006; Huck et al., 2006), atmospheric pressure coverage of the literature to the end of 2006. The review covers MALDI (Creaser & Ratcliffe, 2006). More specific reviews fundamental studies, fragmentation of carbohydrate ions, include those on the analysis of polysaccharides (Cui, 2005), method developments, and applications of the technique to the glycoproteins and attached glycans (Aitken, 2005; Morelle & analysis of different types of carbohydrate. Specific compound Michalski, 2005; Budnik, Lee, & Steen, 2006; Geiser, Silvescu, classes that are covered include carbohydrate polymers from & Reinhold, 2006; Geyer & Geyer, 2006; Harvey, Dwek, plants, N- and O-linked glycans from glycoproteins, glycated & Rudd, 2006; Haslam, Khoo, & Dell, 2006a; Haslam, North, & proteins, glycolipids from bacteria, glycosides, and various other Dell, 2006b; Kondo et al., 2006; Morelle et al., 2006a), natural products. There is a short section on the use of MALDI- N- (Harcum, 2005; Harvey, 2005d,e; Medzihradszky, 2005; TOF mass spectrometry for the study of enzymes involved in Bardor et al., 2006; Jang-Lee et al., 2006) and O-linked glycan processing, a section on industrial processes, particularly (Peter-Katalinic, 2005) glycosylation, bacterial glycoproteomics the development of biopharmaceuticals and a section on the use (Hitchen & Dell, 2005), protein glycation (Lapolla et al., 2006; of MALDI–MS to monitor products of chemical synthesis of Niwa, 2006; Silvań et al., 2006), GPI anchors (Baldwin, 2005), carbohydrates. Large carbohydrate–protein complexes and proteoglycans (Didraga, Barroso, & Bischoff, 2006), glycosyla- glycodendrimers are highlighted in this final section. # 2010 minoglycans (Gama & Hsieh-Wilson, 2005; Pojasek, Raman, & Wiley Periodicals, Inc., Mass Spec Rev 30:1–100, 2011 Sasisekharan, 2005; Sasisekharan et al., 2006), glycosphingoli- Keywords: MALDI; carbohydrates; glycoproteins; glycolipids pids (Levery, 2005; Zheng, Wu, & Hancock, 2006b), and flavonoids (de Rijke et al., 2006). The book on mass spectrometry in biophysics by Kaltashov and Eyles (2005) also contains information. I. INTRODUCTION This review is a continuation of the four earlier ones in this series (Harvey, 1999, 2006, 2009) on the application of MALDI II. THEORY mass spectrometry to the analysis of carbohydrates and glycoconjugates and is intended to bring the coverage of the Knochenmuss (2006) has summarized ion formation mecha- literature to the end of 2006. MALDI continues to be a major nisms in UV MALDI and emphasized that a two-step mechanism technique for the analysis of carbohydrates although electrospray of ionization during or shortly after the laser pulse, followed is becoming increasingly popular. Figure 1 shows the year-by- by secondary reactions in the expanding plume of desorbed year increase in articles reporting use of MALDI for the period material is gaining acceptance. He concludes by saying that: ‘‘To 1991–2006. As the review is designed to complement the earlier the extent that local thermal equilibrium is approached in the work, structural formulae, etc. that were presented earlier are not plume, the mass spectra may be straightforwardly interpreted in repeated. However, a citation to the structure in the earlier work is terms of charge transfer thermodynamics.’’ indicated by its number with the prefix ‘‘1’’ (i.e., 1/x refers to Gas-phase cationization has been demonstrated in an structure x in the first review and 2/x to the second). Other reviews experiment in which two target spots were prepared and and review-type articles directly concerned with, or including illuminated simultaneously with the laser. One spot contained MALDI analysis of glycoconjugates to have been published polyethylene glycol (PEG) and dihydroxybenzoic acid (DHB, during the review period include general reviews on miniatur- 1/26), whereas the other contained DHB and lithium hydroxide. ized separation techniques including LC/MALDI-TOF/TOF Even though the PEG and lithium did not come into contact on the target, [M þ Li]þ ions were observed in the spectrum. However, ———— because of difficulties in removing residual Naþ and Kþ from the *Correspondence to: David J. Harvey, Department of Biochemistry, DHB, the authors could not conclude that gas-phase cationization Oxford Glycobiology Institute, University of Oxford, Oxford OX1 was the only or major process operating under normal MALDI 3QU, UK. E-mail: [email protected] conditions (Erb, Hanton, & Owens, 2006). Mass Spectrometry Reviews, 2011, 30, 1– 100 # 2010 by Wiley Periodicals, Inc. & HARVEY A. High-Pressure and Atmospheric Pressure MALDI (AP-MALDI) Atmospheric pressure MALDI produces ions with less internal energy than vacuum MALDI and has been used to produce spectra of sialylated N- and O-linked glycans and gangliosides without substantial loss of the sialic acid that is a regular feature of vacuum MALDI (Zhang, Fu, & Ning, 2005a). A mixture of DHB and 2,5-dihydroxyacetophenone (DHA, 1/43) was used as the matrix and spectra were recorded with an FT-ICR mass spectrometer. IV. MATRICES A. Theory of Matrix Action FIGURE 1. Number of articles published on the application of Although incorporation of the analyte into the crystal has been MALDI–MS to carbohydrate research by year. thought to be necessary for the MALDI process to occur, a recent study has shown that this probably is not the case and that intimate contact between analyte and the crystal surface is more Sodium cation affinities of hydroxybenzoic acid isomers important. The study showed that the strength of the MALDI have been published (Chinthaka et al., 2006). In general the most signal was approximately inversely proportional to crystal size stable binding conformations involved formation of a hexacyclic suggesting that contact between the analyte and the matrix chelation ring involving the carboxyl carbonyl group and a surface was more important (Trimpin, Ra¨der, & Mu¨llen, 2006). hydroxy group in the 2-position. Proton affinities and gas-phase basicities for the DHB isomers have been calculated using density functional theory and shown to be in good agreement with B. Simple Matrices values obtained by FT-ICR (Rebber et al., 2006). Mesaros et al. (2006) have studied the photophysics of common MALDI 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]mal- matrices and found that 2,4,6-trihydroxyacetophenone (THAP, ononitrile (DCTB, 1) has been shown to be an effective matrix for 1/44) and DHB release heat to the medium more efficiently than hydrophobic compounds but less so for compounds soluble in matrices such as harmane (1/34) and nor-harmane (1/35) and water. Nevertheless, derivatized sugars and glycosides could be þ behave as ‘‘hotter’’ matrices. induced to fly with the formation of the normal [M þ metal] ions The observation that thin MALDI samples can perform (Wyatt, Stein, & Brenton, 2006). differently than thicker samples on metal substrates has been investigated by Knochenmuss, McCombie, and Faderl (2006) for three electrosprayed matrixes, DHB, sinapinic acid (SA, 1/48), and a-cyano-4-hydroxycinnamic acid (CHCA, 1/23), on stain- less steel and gold substrates. Thin sample enhancement was found in both polarities for all three matrices on a steel substrate. Pencil ‘‘lead’’ (a mixture of graphite, clay, and waxes) has On gold, only CHCA showed enhancement. Two models were been shown to be an effective matrix for several types of used to evaluate the data. The first was based on one-photon compound including cyclodextrin. The matrix has the advantage photoelectron emission from the metal, and the second on two- of the absence of low mass matrix ions that characterize the photon matrix ionization at the metal interface. The surface- spectra recorded from most other matrices making it ideal for enhanced matrix photoionization model best fitted the evidence, small molecules although carbon clusters are often seen and, including the fluence-dependence of electron emission from depending on the pencil, various constituents of the ‘‘lead’’ can DHB on steel. give signals (Black et al., 2006). Carbon nanotubes were reported in 2003 as effective matrices for carbohydrates (Xu et al., 2003). However, a problem was keeping them on the MALDI target. This problem has III. INSTRUMENTATION been solved by attaching them to the target with polyurethane adhesive prior to adding the glycan solution (Ren et al., 2005). A pyroelectric lead–lanthanum–zirconate–titanate ceramic This procedure retained the property of the matrix to produce plate has been developed as a MALDI target which allows signals without the low-mass matrix ions. Oxidized carbon spectra of thermally unstable compounds such as carbohydrates nanotubes have been reported to give better results than carbon to be obtained without the use of a matrix (Sato et al., 2005). a- nanotubes themselves because of their greater solubility in water (4/24) and b-cyclodextrins (4/6) in the presence of sodium iodide (Pan et al., 2005). They have been used to record MALDI spectra gave strong [M þ Na]þ ions with no sign of fragmentation. from honeysuckle constituents (Chen et al., 2006c). 2 Mass Spectrometry Reviews DOI 10.1002/mas ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES & Schulz et al. (2006) have compared the degree of analyte liquid matrices 1-methylimidazolium (4 þ 1/23) a-cyano-4- fragmentation in AP-MALDI as a function of the matrix and hydroxycinnamate and tetrabutylammonium (Bu4N þ 1/26) laser fluence.

Load more