DOCSLIB.ORG

Anomeric O-Functionalization of Carbohydrates for Chemical Conjugation to Vaccine Constructs

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Anomeric O-Functionalization of Carbohydrates for Chemical Conjugation to Vaccine Constructs molecules Review Anomeric O-Functionalization of Carbohydrates for Chemical Conjugation to Vaccine Constructs Simon S. Park † ID , Hsiao-Wu Hsieh † ID and Jacquelyn Gervay-Hague *,† Department of Chemistry, University of California, Davis, CA 95616, USA; [email protected] (S.S.P.); [email protected] (H.-W.H.) * Correspondence: [email protected]; Tel.: +1-530-754-9577 † These authors contributed equally to this work. Academic Editors: Paul Kovac, Peng Xu and Helene Pfister Received: 25 June 2018; Accepted: 13 July 2018; Published: 17 July 2018 Abstract: Carbohydrates mediate a wide range of biological interactions, and understanding these processes benefits the development of new therapeutics. Isolating sufficient quantities of glycoconjugates from biological samples remains a significant challenge. With advances in chemical and enzymatic carbohydrate synthesis, the availability of complex carbohydrates is increasing and developing methods for stereoselective conjugation these polar head groups to proteins and lipids is critically important for pharmaceutical applications. The aim of this review is to provide an overview of commonly employed strategies for installing a functionalized linker at the anomeric position as well as examples of further transformations that have successfully led to glycoconjugation to vaccine constructs for biological evaluation as carbohydrate-based therapeutics. Keywords: carbohydrates; glycosylation; glycosides; glycoconjugates; anomeric functionalization 1. Introduction 1.1. Emergence of Glycomics Nucleic acids, proteins and carbohydrates are three important classes of biomolecules. DNA, RNA and the proteins they encode have relatively confined connectivity and predictable chemistries owing to the limited number of ways the nucleic acid and amino acid building blocks can be combined. In contrast, carbohydrates have multiple similarly reactive hydroxyl groups that connect with varying region- and stereochemistries giving rise to a complex set of structures that have no corresponding genetic blueprint [1,2]. With the launch of the Human Genomic Project in the beginning of this century [3,4], efforts have shifted toward understanding structure/function relationships of post-translational modifications of proteins. Glycosylation is a prominent form of post-translational modification occurring in a majority of eukaryotic proteins [5–7]. Other biomolecules such as glycolipids and glycosylphosphatidylinositols (GPI anchor) display hydrophilic carbohydrate moieties that participate in ligand-receptor binding, cell-to-cell interactions and pathogenic processes such as bacterial and viral infection as well as cancer metastasis [8,9]. Deciphering the “sugar codes” created by specific sequences of oligosaccharides linked to lipid and protein anchors is an emerging area of glycomics, which like proteomics has the underlying goal of connecting chemical structures to biological functions. Understanding how structure gives rise to function is critical for the development of carbohydrate-based therapeutics and expedient access to synthetic materials is a significant challenge for researchers in this area. Like most natural products, glycoconjugates are typically difficult to isolate and may only occur as heterogenic mixtures in scarce amounts. Common isolation techniques often Molecules 2018, 23, 1742; doi:10.3390/molecules23071742 www.mdpi.com/journal/molecules Molecules 2018, 23, x 2 of 23 Molecules 2018, 23, 1742 2 of 23 isolation techniques often require enzymatic digestion, detergent extraction and multiple purifications, which may degrade the sugars; although recent methods to extract O-glycans using requirebleach hold enzymatic promise digestion, for commercial detergent use extraction [10]. To address and multiple these limitations, purifications, synthetic which mayplatforms degrade that theafford sugars; large-scale although recentproduction methods of topure extract andO -glycanschemically using defined bleach holdglycoconjugates promise for commercialare under usedevelopment. [10]. To address Chemoenzymatic these limitations, methods synthetic offer platforms a complementary that afford large-scaleapproach; productionhowever, ofenzyme pure andavailability, chemically substrate defined glycoconjugatesspecificity and arescalability under development.can hinder product Chemoenzymatic diversity. methodsIn either offer case, a complementaryachieving the desired approach; stereochemic however, enzymeal specificity availability, and substratemultiplicity specificity of ligation and scalability products canwith hinder high productpurity remains diversity. a challenge In either [11–13]. case, achieving One approach the desired to conjugating stereochemical carbohydrates specificity to andbinding multiplicity partners ofof ligationinterest products(i.e., protein with or high lipid) purity in remainsenantiomer a challengeically pure [11 –form13]. is One through approach the tostereoselective conjugating carbohydratesinstallment of tolinkers binding with partners functionalizable of interest handles, (i.e., protein which or can lipid) be elaborated in enantiomerically to generate pure complex form isglycans through and/or the stereoselectivemultivalent displays. installment of linkers with functionalizable handles, which can be elaborated to generate complex glycans and/or multivalent displays. 1.2. Overview of Glycosylation Principles 1.2. Overview of Glycosylation Principles Carbohydrate synthesis requires a crafty approach in selecting protecting groups, participating groups,Carbohydrate promoter synthesissystems, glycosyl requires donor a crafty and approach selectively in selecting deprotected protecting glycosyl groups, acceptors participating in order groups,to achieve promoter stereo-controlled systems, glycosyl glycosylation donor and in reasonable selectively deprotectedyields [14,15] glycosyl (Figure acceptors1A). The inreactivities order to achieveof the carbohydrate stereo-controlled and glycosylation aglycon partners in reasonable can be finely-tuned yields [14,15 ]by (Figure introducing1A). The different reactivities protecting of the carbohydrategroups. According and aglycon to the partners “arm-disarm” can be finely-tunedconcept introduced by introducing by Fraser-Reid, different protectingelectron releasing groups. Accordingether-type to(i.e., the silyl “arm-disarm” and benzyl) concept protecting introduced groups arm byFraser-Reid, the donor while electron inductively releasing withdrawing ether-type (i.e.,ester silyl (i.e., and acetyl benzyl) and protecting benzoyl) groups disarm arm the the dono donorr [16,17]. while inductivelyDonor leaving withdrawing groups can ester be (i.e., activated acetyl andusing benzoyl) various disarm promoters, the donor which [16,17 are]. Donorcommonly leaving Lewis groups acids can beadded activated in stoichiometric using various or promoters, catalytic whichamounts. are commonlyUpon departure Lewis acidsof the added anomeric in stoichiometric leaving group, or catalyticthe resulting amounts. oxocarbenium Upon departure ion is ofready the anomericfor coupling leaving with group, a glycosyl the resulting acceptor oxocarbenium (nucleophile) ion to is readyform forthecoupling corresponding with a glycosylglycosidic acceptor bond. (nucleophile)When the acceptor to form is the another corresponding carbohydrate, glycosidic oligosa bond.ccharide When synthesis the acceptor results. is another If the carbohydrate, acceptor is a oligosaccharidenon-carbohydrate synthesis aglycon, results. a glyc Ifoconjugate the acceptor is isformed. a non-carbohydrate The stereoselectivity aglycon, aat glycoconjugate the anomeric isposition formed. can The be stereoselectivity influenced by ster at theic hindrance, anomeric positionthe anomeric can be effect, influenced and internal by steric or hindrance,external group the anomericparticipation effect, (such and as internal neighbor-group or external participation group participation or solvent (such effect) as neighbor-group[18,19] (Figures 1B,C). participation NMR is oran solvent essential effect) tool [18used,19] (Figureto determine1B,C). NMRthe anomer is an essentialic stereoselectivity. tool used to According determine to the the anomeric Karplus α β stereoselectivity.equation, α/β-glycosides According are to thecharacterized Karplus equation, by the chemical/ -glycosides shift of are the characterized anomeric proton, by the as chemical well as shift of the anomeric proton, as well as the 3J and 1J coupling constants.[20] Concordantly, the the 3JH,H and 1JC,H coupling constants.[20] H,HConcordantly,C,H the ratio of products is measured by ratiointegration of products of the is anom measurederic proton by integration peaks. of the anomeric proton peaks. (A) Reactivity Regioselectivity Stereoselectivity Promoter PGO (Lewis acid) PGO O + O O O PGO LG HO OR PGO O OR Solvent Glycosyl donor Glycosyl acceptor LA PG: Protecting group O O HOR PGO LG PGO or LG: Leaving group LA: Lewis acid Oxocarbenium ion (B) H (C) LA HOR LA O O O O ACN O PGO LG PGO PGO H PGO LG PGO OR N H 3J = 2-4 Hz O H-H Solvent participation C HOR HOR PGO OR α-glycoside Me H LA 3 O O JH-H = 8-10 Hz O lp - σ* interaction PGO LG PGO β-glycoside O O R O O O R PGO Neighboring-group participation OR Anomeric effect: Stabilization Figure 1. (A) Glycosylation reaction at a glance. (B) Mechanistic overview of α-glycosides. (C) Figure 1. (A) Glycosylation reaction at a glance. (B) Mechanistic overview of α-glycosides. Mechanistic overview of β-glycosides. (C) Mechanistic
Load more

Recommended publications
  • STEREOSELECTIVE GLYCOSYLATIONS and SYNTHESIS of HYALURONAN BIOSYNTHESIS INHIBITORS by Gilbert Ochieng Wasonga a THESIS Submitted
    STEREOSELECTIVE GLYCOSYLATIONS AND SYNTHESIS OF HYALURONAN BIOSYNTHESIS INHIBITORS By Gilbert Ochieng Wasonga A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE CHEMISTRY 2010 1 ABSTRACT STEREOSELECTIVE GLYCOSYLATIONS AND SYNTHESIS OF HYALURONAN SYNTHESIS INHIBITORS By Gilbert Ochieng Wasonga Stereochemical control is an important issue in carbohydrate synthesis. Glycosyl donors with participating acyl protective groups on 2-O have been shown to give 1,2-trans glycosides reliably under the pre-activation based reaction condition. In this work, the effects of additives and reaction solvent on stereoselectivity was examined using donors without participating protective groups on 2-O. We have established that the stereoselectivity could be directed by reaction solvent. The trend of stereochemical dependence on reaction solvent was applicable to a variety of reactions including the selective formation of β-mannosides. In the second part, 3-MeO-GlcNAc is efficiently prepared using a furanose oxazoline intermediate which is well suited for large scale synthesis without the need for extensive column chromatography. In addition, we have developed a robust and rapid procedure for the synthesis of 3-F-GlcNAc derivative required for inhibition studies of hyaluronan biosynthesis. In the course of our synthesis, we have shown the expanded utility of Lattrell-Dax method for carbohydrate epimerization reactions. II ACKNOWLEDGMENTS I would like to thank my advisor Professor Xuefei Huang for his guidance and support that have been instrumental in my graduate studies. Along the way, I have had the opportunity to be mentored by Doctor Youlin Zeng who was a very helpful mentor at the beginning of my chemistry research experience and I will always be grateful to him.
    [Show full text]
  • The First General Electron Transfer Reductions of Carboxylic Acid Derivatives Using Samarium Diiodide
    The First General Electron Transfer Reductions of Carboxylic Acid Derivatives Using Samarium Diiodide A thesis submitted to The University of Manchester for the degree of Doctor of Philosophy In the faculty of Engineering and Physical Sciences 2014 Malcolm Peter Spain School of Chemistry Malcolm Spain PhD Thesis Contents Abstract .................................................................................................................... 5 Declaration................................................................................................................ 6 Copyright statement .................................................................................................. 7 Acknowledgements ................................................................................................... 9 Abbreviations .......................................................................................................... 10 Chapter 1. Introduction ........................................................................................... 13 1.1 Introduction to samarium diiodide .................................................................. 13 1.2 Reduction of ketones and aldehydes ............................................................. 15 1.3 Reduction of carboxylic acid derivatives ....................................................... 23 Chapter 2. Investigations of the SmI2–H2O system ................................................. 27 2.0 Preliminary studies of the SmI2–H2O system ................................................
    [Show full text]
  • Reductions and Reducing Agents
    REDUCTIONS AND REDUCING AGENTS 1 Reductions and Reducing Agents • Basic definition of reduction: Addition of hydrogen or removal of oxygen • Addition of electrons 9:45 AM 2 Reducible Functional Groups 9:45 AM 3 Categories of Common Reducing Agents 9:45 AM 4 Relative Reactivity of Nucleophiles at the Reducible Functional Groups In the absence of any secondary interactions, the carbonyl compounds exhibit the following order of reactivity at the carbonyl This order may however be reversed in the presence of unique secondary interactions inherent in the molecule; interactions that may 9:45 AM be activated by some property of the reacting partner 5 Common Reducing Agents (Borohydrides) Reduction of Amides to Amines 9:45 AM 6 Common Reducing Agents (Borohydrides) Reduction of Carboxylic Acids to Primary Alcohols O 3 R CO2H + BH3 R O B + 3 H 3 2 Acyloxyborane 9:45 AM 7 Common Reducing Agents (Sodium Borohydride) The reductions with NaBH4 are commonly carried out in EtOH (Serving as a protic solvent) Note that nucleophilic attack occurs from the least hindered face of the 8 carbonyl Common Reducing Agents (Lithium Borohydride) The reductions with LiBH4 are commonly carried out in THF or ether Note that nucleophilic attack occurs from the least hindered face of the 9:45 AM 9 carbonyl. Common Reducing Agents (Borohydrides) The Influence of Metal Cations on Reactivity As a result of the differences in reactivity between sodium borohydride and lithium borohydride, chemoselectivity of reduction can be achieved by a judicious choice of reducing agent. 9:45 AM 10 Common Reducing Agents (Sodium Cyanoborohydride) 9:45 AM 11 Common Reducing Agents (Reductive Amination with Sodium Cyanoborohydride) 9:45 AM 12 Lithium Aluminium Hydride Lithium aluminiumhydride reacts the same way as lithium borohydride.
    [Show full text]
  • CHE202 Reductions and Heterocycles
    CHE202 Structure & Reactivity in Organic Chemistry: ! Reduction Reactions and Heterocyclic Chemistry! 9 lectures, Semester B 2014! Dr. Chris Jones! ! [email protected]! Office: 1.07 Joseph Priestley Building! ! Office hours:! 9.30-10.30 am Tuesday! 1.30-2.30 pm Thursday (by appointment only)! Course structure and recommended texts! 2! §" Coursework:! !Semester B – week 9 ! !5% (‘Coursework 7’)! !Semester B – week 11! !5% (‘Coursework 8’)! ! §" Test:! !Semester B – week 12! !15% (‘Test 4’)! §" Recommended text books:! ‘Organic Chemistry’, Clayden, ‘Oxidation & Reduction in ‘Heterocyclic Chemistry’, Greeves & Warren, OUP, 2012.! Organic Chemistry’, Donohoe, Joule & Mills, Wiley, 2010.! OUP, 2000.! Don’t forget clickers! Overview of Reduction Chemistry lecture material! 3! §" Reduction:! - Definition (recap.)! - Reduction of carbon-carbon double and triple bonds! - Heterogeneous hydrogenation! - Homogeneous hydrogenation, including stereoselective hydrogenation! - Dissolved metal reductions! - Other methods of reduction! - Reduction of carbon-heteroatom double and triple bonds! - Reduction of carbonyl derivatives, addressing chemoselectivity! - Stereoselective reduction of carbonyl derivatives! - Reduction of imines and nitriles! - Reductive cleavage reactions! - Hydrogenolysis of benzyl and allyl groups! - Dissolved metal reduction! - Deoxygenation reactions! - Reduction of heteroatom functional groups! e.g. azides, nitro groups, N-O bond cleavage! Reduction: definition! 4! §" Reduction of an organic substrate can be defined as:! - The concerted
    [Show full text]
  • Chemical Modification of Single-Walled Carbon Nanotubes Via Alkali Metal Reduction
    A 677 OULU 2016 A 677 UNIVERSITY OF OULU P.O. Box 8000 FI-90014 UNIVERSITY OF OULU FINLAND ACTA UNIVERSITATISUNIVERSITATIS OULUENSISOULUENSIS ACTA UNIVERSITATIS OULUENSIS ACTAACTA SCIENTIAESCIENTIAEA A RERUMRERUM Elina Pulkkinen NATURALIUMNATURALIUM Elina Pulkkinen Professor Esa Hohtola CHEMICAL MODIFICATION University Lecturer Santeri Palviainen OF SINGLE-WALLED CARBON Postdoctoral research fellow Sanna Taskila NANOTUBES VIA ALKALI METAL REDUCTION Professor Olli Vuolteenaho University Lecturer Veli-Matti Ulvinen Director Sinikka Eskelinen Professor Jari Juga University Lecturer Anu Soikkeli Professor Olli Vuolteenaho UNIVERSITY OF OULU GRADUATE SCHOOL; UNIVERSITY OF OULU, FACULTY OF SCIENCE Publications Editor Kirsti Nurkkala ISBN 978-952-62-1243-2 (Paperback) ISBN 978-952-62-1244-9 (PDF) ISSN 0355-3191 (Print) ISSN 1796-220X (Online) ACTA UNIVERSITATIS OULUENSIS A Scientiae Rerum Naturalium 677 ELINA PULKKINEN CHEMICAL MODIFICATION OF SINGLE-WALLED CARBON NANOTUBES VIA ALKALI METAL REDUCTION Academic dissertation to be presented with the assent of the Doctoral Training Committee of Technology and Natural Sciences of the University of Oulu for public defence in the Arina auditorium (TA105), Linnanmaa, on 15 June 2016, at 12 noon UNIVERSITY OF OULU, OULU 2016 Copyright © 2016 Acta Univ. Oul. A 677, 2016 Supervised by Professor Marja Lajunen Doctor Janne Asikkala Reviewed by Professor Markku Leskelä Professor Mika Pettersson Opponent Professor Tuula Pakkanen ISBN 978-952-62-1243-2 (Paperback) ISBN 978-952-62-1244-9 (PDF) ISSN 0355-3191 (Printed) ISSN 1796-220X (Online) Cover Design Raimo Ahonen JUVENES PRINT TAMPERE 2016 Pulkkinen, Elina, Chemical modification of single-walled carbon nanotubes via alkali metal reduction. University of Oulu Graduate School; University of Oulu, Faculty of Science Acta Univ.
    [Show full text]
  • 2 Reactions Observed with Alkanes Do Not Occur with Aromatic Compounds 2 (SN2 Reactions Never Occur on Sp Hybridized Carbons!)
    Reactions of Aromatic Compounds Aromatic compounds are stabilized by this “aromatic stabilization” energy Due to this stabilization, normal SN2 reactions observed with alkanes do not occur with aromatic compounds 2 (SN2 reactions never occur on sp hybridized carbons!) In addition, the double bonds of the aromatic group do not behave similar to alkene reactions Aromatic Substitution While aromatic compounds do not react through addition reactions seen earlier Br Br Br2 Br2 FeBr3 Br With an appropriate catalyst, benzene will react with bromine The product is a substitution, not an addition (the bromine has substituted for a hydrogen) The product is still aromatic Electrophilic Aromatic Substitution Aromatic compounds react through a unique substitution type reaction Initially an electrophile reacts with the aromatic compound to generate an arenium ion (also called sigma complex) The arenium ion has lost aromatic stabilization (one of the carbons of the ring no longer has a conjugated p orbital) Electrophilic Aromatic Substitution In a second step, the arenium ion loses a proton to regenerate the aromatic stabilization The product is thus a substitution (the electrophile has substituted for a hydrogen) and is called an Electrophilic Aromatic Substitution Energy Profile Transition states Transition states Intermediate Potential E energy H Starting material Products E Reaction Coordinate The rate-limiting step is therefore the formation of the arenium ion The properties of this arenium ion therefore control electrophilic aromatic substitutions (just like any reaction consider the stability of the intermediate formed in the rate limiting step) 1) The rate will be faster for anything that stabilizes the arenium ion 2) The regiochemistry will be controlled by the stability of the arenium ion The properties of the arenium ion will predict the outcome of electrophilic aromatic substitution chemistry Bromination To brominate an aromatic ring need to generate an electrophilic source of bromine In practice typically add a Lewis acid (e.g.
    [Show full text]
  • Carbohydrates: Occurrence, Structures and Chemistry
    Carbohydrates: Occurrence, Structures and Chemistry FRIEDER W. LICHTENTHALER, Clemens-Schopf-Institut€ fur€ Organische Chemie und Biochemie, Technische Universit€at Darmstadt, Darmstadt, Germany 1. Introduction..................... 1 6.3. Isomerization .................. 17 2. Monosaccharides ................. 2 6.4. Decomposition ................. 18 2.1. Structure and Configuration ...... 2 7. Reactions at the Carbonyl Group . 18 2.2. Ring Forms of Sugars: Cyclic 7.1. Glycosides .................... 18 Hemiacetals ................... 3 7.2. Thioacetals and Thioglycosides .... 19 2.3. Conformation of Pyranoses and 7.3. Glycosylamines, Hydrazones, and Furanoses..................... 4 Osazones ..................... 19 2.4. Structural Variations of 7.4. Chain Extension................ 20 Monosaccharides ............... 6 7.5. Chain Degradation. ........... 21 3. Oligosaccharides ................. 7 7.6. Reductions to Alditols ........... 21 3.1. Common Disaccharides .......... 7 7.7. Oxidation .................... 23 3.2. Cyclodextrins .................. 10 8. Reactions at the Hydroxyl Groups. 23 4. Polysaccharides ................. 11 8.1. Ethers ....................... 23 5. Nomenclature .................. 15 8.2. Esters of Inorganic Acids......... 24 6. General Reactions . ............ 16 8.3. Esters of Organic Acids .......... 25 6.1. Hydrolysis .................... 16 8.4. Acylated Glycosyl Halides ........ 25 6.2. Dehydration ................... 16 8.5. Acetals ....................... 26 1. Introduction replacement of one or more hydroxyl group (s) by a hydrogen atom, an amino group, a thiol Terrestrial biomass constitutes a multifaceted group, or similar heteroatomic groups. A simi- conglomeration of low and high molecular mass larly broad meaning applies to the word ‘sugar’, products, exemplified by sugars, hydroxy and which is often used as a synonym for amino acids, lipids, and biopolymers such as ‘monosaccharide’, but may also be applied to cellulose, hemicelluloses, chitin, starch, lignin simple compounds containing more than one and proteins.
    [Show full text]
  • Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments
    A Dissertation Titled: Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides by Pradheep Eradi Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Chemistry ___________________________________________ Dr. Peter R. Andreana, PhD, Committee Chair ___________________________________________ Dr. Steve Sucheck, PhD, Committee Member ___________________________________________ Dr. Jianglong Zhu, PhD, Committee Member ___________________________________________ Dr. Amanda C. Bryant-Freidrich, PhD, Committee Member ___________________________________________ Dr. Cyndee Gruden, Dean College of Graduate Studies The University of Toledo May 2019 Copyright 2019 Pradheep Eradi This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of Total Synthesis of Zwitterionic Bacterial Polysaccharide (PS A1) Antigen Fragments from B. fragilis ATCC 25285/NCTC 9343 with Alternating Charges on Adjacent Monosaccharides by Pradheep Eradi Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Chemistry The University of Toledo May 2019 Zwitterionic polysaccharides (ZPSs) are a relatively new class of carbohydrate antigens, with a paradigm shifting property; they can activate CD4+ T-cells in the absence of lipids, peptide(s) or protein(s) upon MHC class II presentation. Up until now, various anaerobic bacteria are known to express ZPSs, for example, PS A1, PS A2 and PS B (Bacteroides fragilis), Sp1 (Streptococcus pneumoniae), CP5 and CP8 (Staphylococcus aureus) and O-chain antigen (Morganella morgani). Among all the afore mentioned ZPSs, Sp1 and PS A1 polysaccharides were the prime focus of research for the past few decades and their biological properties are very well-understood.
    [Show full text]
  • A Versatile Glycosylation Strategy Via Au(III) Catalyzed Activation of Thioglycoside Donors† Cite This: Chem
    Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue A versatile glycosylation strategy via Au(III) catalyzed activation of thioglycoside donors† Cite this: Chem. Sci.,2016,7,4259 Amol M. Vibhute, Arun Dhaka, Vignesh Athiyarath and Kana M. Sureshan* Among various methods of chemical glycosylations, glycosylation by activation of thioglycoside donors using a thiophilic promoter is an important strategy. Many promoters have been developed for the activation of thioglycosides. However, incompatibility with substrates having alkenes and the requirement of a stoichiometric amount of promoters, co-promoters and extreme temperatures are some of the limitations. We have developed an efficient methodology for glycosylation via the activation of thioglycoside donors using a catalytic amount of AuCl3 and without any co-promoter. The reaction is Received 10th February 2016 very fast, high-yielding and very facile at room temperature. The versatility of this method is evident from Accepted 4th March 2016 the facile glycosylation with both armed and disarmed donors and sterically demanding substrates DOI: 10.1039/c6sc00633g (acceptors/donors) at ambient conditions, from the stability of the common protecting groups, and from www.rsc.org/chemicalscience the compatibility of alkene-containing substrates during the reaction. Creative Commons Attribution 3.0 Unported Licence. Introduction alkenes;8 and (iv) the requirement of extremely low temperatures for the reaction. Development of novel and milder methods of Various forms of carbohydrates play important biological roles thioglycoside activation that overcome these limitations is an 5 ,6 and hence the chemical synthesis of glycoconjugates and agenda of utmost importance among chemists. g a Pohl et al.
    [Show full text]
  • AP Biology Summer Assignment Holy Spirit Prep 2019
    AP Biology Summer Assignment Holy Spirit Prep 2019 Textbook: “Principle of Life” 2nd edition, for the AP course 2018 Chapters 1-3 (pages 1-59) This summer assignment will cover the introduction to biology, chemistry of life, and essential macromolecules for life. The concepts covered in these chapters are either review from previous classes or relatively easy enough to allow you to work through them on your own. The more complex connections between these chapters will be discussed during the first two weeks of the school year. Biozone Workbook: “AP Biology 1” Student edition, 2nd edition 2017 and Biozone Workbook: “AP Biology 2” Student edition, 2nd edition 2017 Read each chapter in the text book, answer all the questions listed below, and complete the corresponding pages in the biozone workbooks covering those topics. The answers can be typed or handwritten for the questions below and written in the workbook for the biozone pages listed. Do not tear out the biozone workbook pages. I will check your answers directly from the workbook. This assignment will be due on Wednesday, Aug 21, 2019. We will have a test over the material during the second week of the school year. For questions, contact Mr. Harrison at [email protected] Chapter 1: Principles of Life Answer the following: 1. Organisms share many conserved biological, chemical, and structural characteristics. Briefly outline the 8 distinctive characteristics of life shared by all living organisms. 2. How do the shared characteristics on your list (in #1) provide evidence for evolution? 3. There are several competing hypotheses about the evolution of early life on Earth, but as life evolved, all cells clearly had requirements for raw materials and energy transfers.
    [Show full text]
  • Aerospace Medicine & Biology Space Medicine & Biology Aero 9
    Aerospace Medicine NASA SP-7011 (232) and Biology May 1982 IWNSA A Continuing Bibliography with Indexes (NASA-SP-701 1 (232) ) AT. CE MEDICINE AND N82-2898U BIOLOGY: A CONTINUING BIBLIOGRAPHY WITH INDEXES (SUPPLEMENT 232) (National Aeronautics and Space Administration) 137 p Unclas Hc <7.QQ CSCL Ofa£ 00/52 25483 National Aeronautics and Space Administration Aerospace Medicine & Biology space Medicine & Biology Aero 9 Medicine & Biology Aerospao dicine & Biology Aerospace M ne & Biology AerosjatoiMedici Biology Aerospace Medicine & gy Aerospace Medicine & Biolo 3rospace Medicine & Biology / pace Medicine & Biology Aeros Medicine & Biology Aerospace cine & Biology Aerospace Med & Biology Aerospace Medicine < ACCESSION NUMBER RANGES Accession numbers cited in this Supplement fall within the following ranges. STAR (N-10000 Series) N82-16040 - N82-18118 IAA (A-10000 Series) A82-18840 - A82-22250 This bibliography was prepared by the NASA Scientific and Technical Information Facility operated for the National Aeronautics and Space Administration by PRC Government Information Systems. NASA SP-7011(232) AEROSPACE MEDICINE AND BIOLOGY A CONTINUING BIBLIOGRAPHY WITH INDEXES (Supplement 232) A selection of annotated references to unclassified reports and journal articles that were introduced into the NASA scientific and technical information sys- tem and announced in April 1982 in Scientific and Technical Aerospace Reports (STAR) International Aerospace Abstracts (IA A). Scientific and Technical Information Branch 1982 National Aeronautics and Space Administration Washington, DC NASA SP-7011 and its supplements are available from the National Technical Information Service (NTIS). Questions on the availability of the predecessor publications, Aerospace Medicine and Biology (Volumes I - XI) should be directed to NTIS. This supplement is available as NTISUB/123/093 from the National Technical Information Service (NTIS), Springfield, Virginia 22161 at the price of $7.00 domestic; $14.00 foreign.
    [Show full text]
  • Effect of Glycosylation on Protein Folding: a Close Look at Thermodynamic Stabilization
    Effect of glycosylation on protein folding: A close look at thermodynamic stabilization Dalit Shental-Bechor and Yaakov Levy* Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel Edited by Jose´N. Onuchic, University of California at San Diego, La Jolla, CA, and approved May 1, 2008 (received for review February 10, 2008) Glycosylation is one of the most common posttranslational mod- ical functioning of proteins in the cell. Understanding the effects ifications to occur in protein biosynthesis, yet its effect on the of posttranslational modifications to the protein energy land- thermodynamics and kinetics of proteins is poorly understood. A scape is valuable in understanding protein function and how minimalist model based on the native protein topology, in which protein thermodynamics and kinetics can be modulated by the each amino acid and sugar ring was represented by a single bead, formation of a conjugate or through an external stimulus. In this was used to study the effect of glycosylation on protein folding. article, we explore the effects of glycosylation on the biophysical We studied in silico the folding of 63 engineered SH3 domain properties of proteins with the main goal of understanding variants that had been glycosylated with different numbers of folding mechanisms, thermodynamics, and kinetics in the conjugated polysaccharide chains at different sites on the protein’s context of the cell. surface. Thermal stabilization of the protein by the polysaccharide Glycosylation [i.e., the attachment of polysaccharide chains chains was observed in proportion to the number of attached (also termed ‘‘glycans’’) to proteins] is regarded as one of the chains.
    [Show full text]