Click chemistry in glycoscience new developments and strategies

CLICK CHEMISTRY IN GLYCOSCIENCE CLICK CHEMISTRY IN GLYCOSCIENCE New Developments and Strategies Edited by ZBIGNIEW J WITCZAK ROMAN BIELSKI Copyright C 2013 by John Wiley & Sons, Inc All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 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United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002 Wiley also publishes its books in a variety of electronic formats Some content that appears in print may not be available in electronic formats For more information about Wiley products, visit our web site at www.wiley.com Library of Congress Cataloging-in-Publication Data: Click chemistry in glycoscience : new developments and strategies / edited by Zbigniew J Witczak, Roman Bielski p ; cm Includes bibliographical references and index ISBN 978-1-118-27533-7 (cloth) I Witczak, Zbigniew J., 1947- II Bielski, Roman, 1946[DNLM: Glycoconjugates–chemistry Click Chemistry–methods Glycoconjugates–physiology QU 75] 572 567–dc23 2012040254 Printed in the United States of America ISBN: 9781118275337 10 CONTENTS FOREWORD vii PREFACE ix CONTRIBUTORS xiii LIST OF ABBREVIATIONS xvii I CLICK CHEMISTRY STRATEGIES AND DECOUPLING Paradigm and Advantage of Carbohydrate Click Chemistry Strategy for Future Decoupling Roman Bielski and Zbigniew J Witczak II THIO-CLICK CHEMISTRY OF CARBOHYDRATES Thio-Click Chemistry in Glycoscience: Overview and Perspectives 33 Zbigniew J Witczak Free-Radical Thiol-ene and Thiol-yne Couplings as Click Processes for Glycoconjugation 45 Alessandro Dondoni and Alberto Marra v vi CONTENTS III CARBOHYDRATE CLICK CHEMISTRY FOR NOVEL SYNTHETIC TARGETS The Development and Application of Clickable Lipid Analogs for Elucidating and Harnessing Lipid Functions 79 Michael D Best Clicking Sugars onto Sugars: Oligosaccharide Analogs and Glycoclusters on Carbohydrate Scaffolds 107 Maria Laura Uhrig and Jos´e Kovensky Click Multivalent Glycomaterials: Glycoclusters, Glycodendrimers, Glycopolymers, Hybrid Glycomaterials, and Glycosurfaces 143 Carmen Ortiz Mellet, Alejandro M´endez-Ardoy, and Jos´e Manuel Garc´ıa Fern´andez Toward Imaging Glycotools by Click Coupling 183 Yves Chapleur, Christine Vala, Franc¸oise Chr´etien, and Sandrine Lamand´e-Langle Bioorthogonal Reactions for Labeling Glycoconjugates 211 Fr´ed´eric Friscourt and Geert-Jan Boons “Sweet” Sucrose Macrocycles via a “Click Chemistry” Route 235 Mykhaylo A Potopnyk and Sławomir Jarosz IV CARBOHYDRATE CLICK CHEMISTRY IN BIOMEDICAL SCIENCES 10 Neoglycoprotein Synthesis Using the Copper-Catalyzed Azide–Alkyne Click Reaction and Native Chemical Ligation 253 Joanna M Wojnar, Dong Jun Lee, Clive W Evans, Kalyaneswar Mandal, Stephen B H Kent, and Margaret A Brimble 11 Biomedical Applications of “Click”-Modified Cyclodextrins 271 Zhenshan Jia, Rakesh K Singh, and Dong Wang 12 Triazolyl Glycoconjugates in Medicinal Chemistry 293 Rama Pati Tripathi, Pratibha Dwivedi, Anindra Sharma, Divya Kushwaha, and Vinod Kumar Tiwari 13 Click Chemistry Applied to Carbohydrate-Based Drug Discovery 325 Vanessa Leiria Campo and Ivone Carvalho INDEX 359 FOREWORD This book, compiled by Zbigniew Witczak and Roman Bielski, brings together contributions from authors around the world in addressing the impact of a single chemical reaction that permits the covalent connection of two complex precursor molecules under mild conditions The reaction has found wide application in the fields of carbohydrate chemistry and glycobiology for building complex glycoconjugate target structures of interest in many biomedical areas The particular reaction is the (3 + 2) 1,3-dipolar cycloaddition of an alkyne to an azide at room temperature under copper(I) catalysis to generate a 1,2,3-triazole Since its initial discovery by Huisgen in 1963, there have been numerous publications where it has been employed for a multitude of purposes, including applications in the carbohydrate field that date back to the 1970s However, it was not until the beginning of the present millennium that an “explosion” of research on the scope of this reaction began after Sharpless, and independently, Meldal, employed this procedure for the rapid synthesis, through heteroatom links, of many useful new compounds, peptide conjugates, and combinatorial libraries At that point in time, the awkward formal name of Huisgen’s excellent reaction was whimsically dubbed “click” chemistry, presumably because the simplicity of the reaction could be likened to the ends of a bracelet being “clicked” together The same concept of covalently connecting two complex molecules under very mild conditions has more recently led to valuable new procedures that also meet the “click” reaction criteria These include the photoinduced reaction between a thiol and either an alkene or an alkyne, and the coupling between a thiol and a Michael enone acceptor The 13 chapters in the Witczak–Bielski book bring together a wide range of applications of these ligation strategies directed toward carbohydrate-based targets, vii viii FOREWORD including various types of glycoconjugates, such as neoglycoproteins, glycoclusters, glycodendrimers, and cyclodextrin conjugates The reaction offers potential in diverse biomedical areas, including synthetic antigens, analogs of cell-surface receptors, immobilized enzymes, targeted drug delivery systems, multivalent cancer vaccines, and many others Beyond the original Huisgen reaction, there now have evolved several variants, some involving modifications of the original alkyne and azide reactants, along with such adaptations as novel catalysts for effecting the reaction under the mildest conditions, and performing the ligation reaction in vivo Many of these extensions are detailed in different chapters in the book, together with the thiol–alkene, thiol–alkyne, and thiol–enone conjugation reactions that also merit the “click” designation This book derives from presentations made in a 2011 symposium at a meeting of the American Chemical Society Not all relevant literatures on the alkyne–azide cycloaddition are documented With new work being published almost daily, the coverage, even in the carbohydrate field alone, can never be complete Nevertheless, the compilers of this volume have made a valuable contribution by bringing together the collective efforts of more than 30 researchers working on the applications of “click” chemistry to numerous targets in the carbohydrate and glycoconjugate area The book provides a valuable resource for both the specialist researcher and the general reader Derek Horton Professor of Chemistry Emeritus Ohio State University PREFACE Synthesis of compounds designed to fulfill special requirements or exhibit specific properties has belonged and will belong to the most important targets of organic chemistry This area of synthesis, particularly when applied to synthesis of constructs containing carbohydrates, has experienced a dramatic acceleration in recent years One factor explaining the observed acceleration has been a better understanding of the function and structure of glycoproteins and other naturally occurring sugar derivatives Another factor, perhaps even more significant, is the introduction of the concept of click chemistry by Finn, Kolb, and Sharpless, which dramatically facilitated the formation of various constructs Chemistry of carbohydrates containing molecules has benefited tremendously from the introduction of this concept The presented book attempts to offer an insight into the new developments created by marrying click and carbohydrate chemistries Carbohydrates represent a unique family of polyfunctional compounds that can be chemically or enzymatically manipulated in a multitude of ways They have been extensively used as starting materials in enantioselective synthesis of many complex natural products with a plurality of chirality centers Synthetic organic chemistry that utilizes these carbohydrate building blocks continues to spawn revolutionary discoveries in medicinal chemistry, pharmacology, molecular biology, glycobiology, and medicine simply by providing not only the raw material but also the mechanistic insight of modem molecular sciences ix x PREFACE Click chemistry was introduced over 10 years ago Its founders offered the following description: A click reaction must be modular, wide in scope, high yielding, create only inoffensive by-products (that can be removed without chromatography), are stereospecific, simple to perform, and that require benign or easily removed solvent Since then, Sharpless’ concept of click chemistry was quickly transplanted to carbohydrate chemistry and the number of publications in the field has been steadily growing This book originates from the symposium “Click Chemistry Approaches in Carbohydrate Chemistry,” which we organized during the 242nd Meeting of the American Chemical Society in Anaheim in Spring 2011 It attracted several prominent speakers, had a relatively large attendance, and was met with a lot of interest Some of the chapters in this book are based on the presentations delivered at the symposium Other contributions are also from leading experts in the field of carbohydrate chemistry Some of the chapters are reviews of the recent literature; some describe recent experiments performed at the authors’ laboratories We believe that all the articles are of very high standard and offer a novel perspective on the discussed subjects The medical and biomedical applications of synthetic organic chemistry were probably more affected than any other area of research (perhaps with the exception of polymer chemistry) by the development of click chemistry Thus, it is not surprising that almost all of the chapters in the book are to some extent concerned with such applications It confronts the editors with a dilemma that is impossible to address satisfactorily – how to divide the book into consistent segments By no means are we satisfied with our choice but some kind of division had to be introduced Thus, the reader should not be surprised finding biomedical applications described in segments carrying a title suggesting that the emphasis was put on an entirely different topic Each chapter in the book covers issues related to click chemistry and glycoconjugation, and discusses synthetic methodologies and potential applications of the synthesized constructs In the last few years, it has been documented that the addition of thiols to unsaturated compounds is a legitimate click process Thus, we made sure that this type of click reactions is represented in the book together with the most popular click reaction, that is, 1,3-dipolar addition of azides to alkynes The topics covered in the book are grouped into four categories: Click chemistry strategies Thio-click chemistry of carbohydrates Click chemistry related to life science and glycobiology Click chemistry related to medicinal chemistry The introductory chapter written by both editors of the volume discusses the important aspects of carbohydrate click chemistry methodologies and proposes a novel strategy applicable to synthesizing certain glycoconjugates PREFACE xi Chapter authored by Witczak deals with thio-click strategies employed to the synthesis of thiodisaccharides and other sulfur-bridged oligosaccharide scaffolds Interestingly, the most efficient methodologies compiled in this review were developed before the official birth of thio-click chemistry Chapter authored by Dondoni and Marra describes intriguing results of the experiments employing various thio-click glycoconjugation processes The development and application of clickable lipid analogs for elucidating and harnessing lipid function were thoroughly explored by Best in Chapter The chapter discusses most types of natural molecules, including nucleic acids, proteins, various lipids, and many substituted glycerols and, of course, carbohydrates In Chapter 5, Uhrig and Kovensky review the important topic of syntheses of oligosaccharide analogs and glycoclusters on carbohydrate scaffolds Mellet and coworkers offer in Chapter a different perspective on the closely related subject of click multivalent glycomaterials, including glycosurfaces, glycodendrimers, and glycopolymers Chapter by Chapleur and coworkers addresses clickable formation of carbohydrates labeled with radiotracers for molecular imaging Chapter by Friscourt and Boons is a very broad review of bio-orthogonal reactions for labeling glycoconjugates The review discusses the processes belonging to click chemistry as well as other important coupling reactions, such as Staudinger ligation and labeling with photoactivatable sugars Potopnyk and Jarosz explore in Chapter quite a new topic of click functionalization of sucrose in the synthesis of interesting sucrose-based macrocycles Brimble and coworkers contribute in Chapter 10 with a discussion of novel syntheses of neoglycoproteins via copper-assisted azide–alkyne click reaction and native chemical ligation Chapter 11 by Wang and coworkers describes the formation and new fascinating biomedical applications of “click-modified” cyclodextrins In Chapter 12, Tripathi, Tiwari, and coworkers explore the important applications of triazolyl glycoconjugates in medicinal chemistry The review highlights the synthesis of prototypes of drug molecules with high chemotherapeutic potential Finally, Chapter 13 by Campo and Carvalho provides a general overview of the potential applications of click reactions in the synthesis of highly valuable, bioactive, carbohydrate-based ligands for lectins, antitumor vaccines, and various enzyme inhibitors With the increasing complexity of modern sciences in the twenty-first century, a need to educate industrial leaders, public, and governmental funding agencies about the intellectual and technical potential and economic importance of specific areas of life sciences has become more and more crucial One such area is the part of glycoscience emerging as a result of a marriage between the concepts of click and carbohydrate chemistries We hope that this book will fill this need, at least to some extent In conclusion, we believe the presented collection of articles offers an insight into the present stage of click-based glycosciences and will help steer future discoveries to fulfill the enormous potential in the area of click carbohydrate chemistry INDEX Fluorescein isothiocyanate-labeled avidin FITC-avidin, 217 Fluorescein labeling, fluorolabeling, 70, 71 Fluorescence, 219 Fluorescence assay, 350 Fluorescence enhancement, 281 Fluorescence microscopy, 84, 86 Fluorescence quenching, 162 Fluorescence recovery after photobleaching (FRAP), 94 Fluorescence self-quenching induced by ConA, 162 Fluorescence sensor molecules, 282 Fluorescent dansyl label, 86 Fluorescent dansyl residue, 122 Fluorescent label (tag), 85, 88 Fluorescent NBD-PE conjugate, 85 Fluorescent sensors, 282 Fluorescent TAMRA-alkyne, 97 Fluorescent transformation, 282 Fluorocholine (FC), 185 Fluorogenic azidocoumarin, 85 Fluorogenic phosphine, FRET-based, 219 Fluorogenic probes, click-activated, 221 Fluorophore, 94 Fluorophore 8-anilino-1naphtalenesulfonate, 124 Fluorophore-tagged liposomes, 84 Fluorophosphonate, 97 N-Fmoc-propargyl glycine, 191 N-Fmoc-protected dipeptide, 63 Fmoc-Ser-OH, Glycosylation of, 205 Făorster resonance energy transfer (FRET), 82 “Fructose end”, 243 Fructosyl amine, 201 Fucose, modified, 216 Fucosyl transferases (Fuc-T), 216, 338 Fucosylated glycans, 220 ␣1,3FucT, 217 Fullerenes, 165 Functional biomaterials, 273 Functionalization of membrane surfaces, 81 Galabiose, 238 D-galactal triacetate, 51 ␤-D-Galactopyranosides, azidoalkyl, 164 Galactopyranosides, azido-functionalized, 152, 164 365 ␤-D-Galactopyranosyl glycodendrimers, 152, 154 Galactosamine, 237 Galactose, 9, 15, 54, 327 ␤-D-Galactose, 121 ␤-D-Galactose-(1→3)-␣-D-N-acetylgalactosamine, 257 ␤-Galactose-binding lectin, 85 Galactose-derived alkene, 48 ␤-Galactosidase inhibitors, 312 S-Galactoside epitopes, 138 Galactosylazide, 194 Galactosylmethyl azide, 54 Galactosyltransferase enzyme, engineered, 216 Galatriose, 238 ␣-GalCer, 298 Galectin-3, 328 Galectins, 108, 301, 326, 327 GalNAc-N3, 263, 264 Gaucher disease, 343 GDP-Fucose, 303, 338, 340 S-geranylgeranyl, 98 Gene delivery carriers, 283 GFP + breast cancer cells, 290 O-GlcNAc transferase, 216 Glucose-6-phosphatase inhibitory activity, 312 Glucosidase inhibitors, 342 Glucosidases, 342 Glucosylceramide synthase (GCS) inhibitors, 342 S-glucosyl glutathione, 65 Graft copolymers, 278 GDP-6-alkynylfucose GDP-FucAl, 217 GDP-fucose, 216 Gene expression, inhibition, 199 D-glucal, 51 D-glucal triacetate, 50 Gluconic acid, 237 ␣-D-Glucopyranoside units, 271 ␤-D-Glucopyranosyl azide, peracetylated, 159 Glucosamine, 239 ␤-D-Glucose, 121 Glucose, 9, 15, 54, 239 conjugated c(RGDf), 189 -derived alkyne, 145 -peptide conjugate, 203 366 INDEX ␣-Glucosidase inhibitory activity, 312 Glucosyl thiol, 50, 67 ␤-D-glucosyl thiol, 54 peracetylated, 50, 63 -triazolo-alanine, 193 Glucosylated bis-triazolo-amine, 194 Glucosylated 2-nitroimidazole, 204 Glucothione, sodium salt, 14 Glucothiose, 11, 15 Glucuronic acid, 18 GLUT transporters, 184 Glutamic acid, 65 Glutathione, 203 Glutathione Glu-Cys-Gly, 65 Glutathione-based S-glycopeptide, 65 Glycal, 51 Glycan, 211, 212, 213, 253, 254, 265 Glycan, array technologies, 212 identification, 215 mapping, 222 structures, mass spectrometric profiling, 212 Glycan trafficking, 222 Glycan-binding proteins, 212 Glycan, biotinylated, 222 Glycan–peptide linkages, unnatural, 255 Glycan–protein link, 254 Glycan, isobaric nature of, 212 metabolically labeled, 213 mucin-type, 215 permethylated, 212 Glycerolipid, 81 Glycinamide, bis-propargylated, 193 Glycinyl group, 62 Glycoamino acid triazole-linked, 256 Glycoamphiphiles, diacetylenic, 161 Glycoarray technology, 170, 212 Glycobiology, 164 Glycocalyx, 59, 143, 228 Glycoclusters, 47, 131, 134, 137, 139, 171 conformationally locked, 149 low valency, 144 multimannoside, 144 Glyco-CNTs, multivalent, 167, 168 Glycocoating of functionalized scaffolds, 144 Glycocoating, 167 Glycoconjugates, 108, 131, 222, 223, 318 alkyne containing, 216 azido containing, 216 benzene sulfonamides, 238 biosynthesis, 229 cell surface, 215 LacNAc-containing, 216 octavalent, 55 of living cells, 213 pentavalent, 166 protein complexes, 227 Glycoconjugation, 164 Glycoconjugation of radiotracers, 190 Glycocyclodextrins, 121 Glycodendrimers, 47, 59, 61, 152, 131, 169, 170, 304 octavalent galactose-conjugated, 167 octavalent lactose-conjugated, 167 octavalent mannose-conjugated, 167 Glycodendrimers, Ru(II)-centered, 152, 156 Glycodendron, 59, 152, 155, 171 Glycodendron–core multiconjugation, 152 Glycodendrons, trivalent galactosyl, 167, 169 Glycoenzymes, 212 Glycofluorenyl monomers, 162 Glycoforms, 254 Glycofullerenes, di or dodecavalent, 166 Glycogen phosphorylase, 173 Glyco-gene microarray technology, 212 Glycoligands, C-linked, 148 Glycoligands, N-linked, 148 Glycolipids, 143 Glycolipids antigens, 334 Glycoliposomes, 161 Glycolysation of the Lys residue, 202 Glycomacrocycles, 351 Glycomaterials, hybrid, 164 Glycomaterials, silica based, 169 Glycomics, 212 Glycomimetic clusters, 173 Glycomimetics, 47, 59, 131, 173, 331 Glyconanomaterials, 164, 167 inorganic-organic hybrid core, 169 Glyconanoparticles, 161 Glyconanoparticles (ZnS/CdSe), 167 Glyconanotechnology, 164 Glycooligomers, 171 C-glycopeptide, 68 INDEX S-glycopeptide, 65 Glycopeptide mimetics, 255 Glycopeptides, 47, 62, 202, 215, 254, 335, 336 homogenous, 254 labeled, 189 resin bound, 222 Glycopolymer-coated microporous membranes, 159 Glycopolymer:DNA:lectin ternary complexes, 164 Glycopolymers, 131 Glycopolymers, alkyne functionalized, 171 Glycopolymers, amphiphilic, 161 Glycopolymers, bead-immobilized, 158 Glycopolymers, click, 153 Glycopolymers, fluorescent, 156, 162, 163 Glycopolymers, galactosylated, 159 Glycopolymers, maleimide-terminated, 157 Glycopolymers, mannosylated, 159 Glycopolymers, multivalent, 154 Glycopolymers, polycationic, 164 Glycopolymers, sulfated, 159 Glycoprotein identification, 222 Glycoprotein mimetics, 255 Glycoproteins, 131, 143, 154, 163, 211, 214, 222, 226, 235, 255 Glycoproteins, cellular, 228 Glycoproteins, mature, 212 Glycoproteins, sialylated, 215 Glycosamide scaffolds, 131 Glyco–SAMs, 171 Glycosensors, 145 O- and N-glycosidase, 62 N-glycosidase F PNGase, 222 Glycosidase inhibitors, 108 Glycosidase inhibitory activity, 173 Glycoside cluster effect, 166, 329, 333 Glycoside–peptide linkage, 267 C-Glycosides, 119 N-glycosides, 211 C-Glycosides, alkyne-armed, 147 C-Glycosides, azide-armed, 147 Glycosides, azido-functionalized, 256 C-Glycosidic, 70 Glycosidic bond, 255 Glycosilicas, 170 Glycosphingolipids, 342 Glycosurfaces, 170 367 S-glycosidic, 70 N-glycosylation of imidazole, 204 S-glycosylated protein, 64 Glycosyl alkyne, 256 Glycosyl amino acids, 47 S-glycosyl amino acids, 62, 64 Glycosyl azide, 113, 256, 265, 267 Glycosyl partners, 265 Glycosyl thiol, 33, 35 Glycosylation, 52, 68, 200, 204, 253, 254, 266 Glycosylation, Congenital Disorders of, 211 Glycosylation, in eukaryotes, 253 Glycosylation, site-selective, 255 3-C-Glycosyl-1,2,4-oxadiazole motif, 173 Glycotopes, 148, 152 Golgi complex, 211, 212 Guanidine hydrochloride, 261 D-gulal, 51 ,2,3,3 ,4,4 -Hexa-O-benzylsucrose, 240 H9c2(2-1) cells, 284 Hdj-2, 99 HeLa cells, 86, 284 Helicobacter pylori ␣1,3fucosyltransferase, 216 Hemagglutination inhibition assay (HIA), 166 Hemagglutinin-mediated adhesion, 52 Heparosan, unnatural, 237 Hepatocytes, 164 Hepatocyte-specific gene delivery, 165 Heptakis-(6-deoxy-6-azido)-␤-CD, 275 Hepta-O-␤-D-galactopyranosides, 148 Hepta-O-␤-lactosides, 148 Heptavalent glycocyclodextrins, 122 Hepta-O- and S-␣-D-mannopyranosides, 148 Heptyl ␣-D-mannopyranoside, 147 Heterocluster effect, 156 Heteroglycoclusters, 145, 146, 156 Heteroglycopolymers, 155, 157 Heteroglycopolymers, fluorescently labeled, 157 Hexokinase, 96 Highly branched, 14 High-mannose N-glycans, 151 HIV infection, 158 HIV-neutralizing antibody 2G12, 151 368 INDEX Homeostasis of calcium, 288 Homoallylglycine, 64 Homopropargyl [18 F]fluoride, 196 Homopropargyl alcohol, 195 Homopropargylglycine (Hpg), 262 HPLC, 83 Huisgen 1,3-dipolar cycloaddition (HDC), 4, 5, 8, 108, 220, 273 Human immunodeficiency virus, (HIV), 342 Human prion protein, 86 Hyaluronan (HA)-based hydrogels, Hydrogel, 279 Hyperbranched polyglycerols (HPGs), 333 Hydroxyapatite, nanostructured, 170 2-[2-(2-Hydroxyethoxy)-ethoxy]-1ethanethiol, 57 2,2-bis(Hydroxymethyl)propionic acid (bis-MPA, 152 4-Hydroxynonenal, 100 Hyperbranched glycopolymers, 14 Hyperbranched hyperglycerol, ␤-galactopyranosyl-coated, 160 Hypoxia, 204 Imaging glycotools, 183 Imaging, medical, 183 Imaging, molecular, 183, 197, 199 Imidacloprid, 282 Iminosugar 1-deoxynojirimycin (DNJ), 173 Iminosugars, 345 Immune response, 107, 129 Immunoelectron microscopy, 94 Immunostimulants, 91 111 In-1,4,7,10-tetraazacyclododecane1,4,7,10-tetraacetic acid, 192 Inclusion complexes, 271 Infection, bacterial, 143 Infection, viral, 143 Inflammation, 129, 329 Influenza A virus, 52, 308 Influenza, prophylaxis, 173 Inhibitors of ␣-glucosidase, 113 ␣v ␤3 Integrin, 191, 192 Integrin, heterodimeric transmembrane proteins 191 Integrin-targeting ligand, 85 Intercellular membranes, 94 Interleukin-8 IL-8, N-terminal serine of, 226 S-isosteres, 48 Isosteric linkage, 255 Isothermal calorimetry, 136 Isozymes hCA I, II, and IX, human, 238 Jurkat cells, 217, 228 KD values, 52 KD20, cell line, 228 Kessler’s peptide c(RGDfV), 192 Keto-DIBO, 224 Ketones as chemical reporters, 214 Keyhole limpet hemocyanin (KLH), 298, 334 Koenigs–Knorr conditions, 205 KRN7000 analog, 41 Labeled carbohydrates, 187 Labeling of glycoconjugates, bioorthogonal, 213 Labeling, metabolic, 227, 228 LacNAc unit, 216 Lactose/galactose-specific lectin peanut agglutinin (PNA), 146 Lactoside, 329 ␤-Lactoside, 118 Lactoside epitopes, 134 Lactosyl clusters, per-(O-2,O-3)substituted, 148 S-lactosyl peptide, 66 Lactosyl thiol, peracetylated, 63 Lactosyl thiols, 58, 66 Laser desorption ionization-mass spectrometry (LDI-MS), 19 Lawesson’s reagent, 37, 38 LC-MS/MS identification, 97 Lec2 cells, 216 Lectin, 52, 54, 59, 143, 253 Lectin array technologies, 212 Lectin Concanavalin A, 82, 146 Lectin PA-IL, 149 Lectin recognition, 157 Lectin, FimH, 147 Lectin, human dendritic cell-associated, 158 Lectin, PA-IL lectin, 166 Lectin, recombinant rat mannose-binding (MBL), 157 Lectin-binding affinity, 146 INDEX Lectin-binding properties, 164 Lectin-type membrane receptors, Leishmania mexicana, 341 Leishmania, 340, 341 Leukocyte trafficking, 329 Leukocyte-derived selectins, 159 L-Fucose, 303, 331, 338 Ligand-receptor binding system, 278 Ligation, 144 Ligation chemoselective, 187, 213 Linear synthesis, 254, 255 Linker stability, 274 Lipase, 17 Lipase AS Amano, 17 Lipid, 108 Lipid acyl chains functionalization, 88 Lipid scaffold, 85 Lipidated peptide fragment, 86 Lipidation, 80, 81 Lipid-binding proteins, 95 Lipid-modifying proteins, 95 Lipids, biotinylated, 86 Lipids, fluorescence-tagged, 86 Lipoic acid ligase, 100 Lipopeptides, 86 Lipophilicity, 200 Lipopolysaccharide effects, 148 Lipopolysaccharides (LPS), 338 Liposome–liposome binding, 84 Lissamine-rhodamine-tagged PE, 82 Lovastatin, 99 Lung cancer cells, 167 Lutidine, 246 Lymphocyte trafficking, 338 Lysine, ␻-terminus of, 201 Lysophosphocholine (LPC), 95 Lysosomal storage diseases, 342 Macrocyclic skeleton, 239 Magnetic resonance, 183 Magnetic resonance Imaging (MRI), 315 Maillard reaction, 200, 201, 202 MALDI-TOF spectrometry (analysis), 56, 68, 70 Maleimide, 203 Maltosides, dipropargylated, Maltotriose, glycosylation with, 202 ManNAc Ac5ManNTGc, 228 ManNAz, 218 369 ManNDAz, peracetylated, 228 Man3GlcNAc2 core structure, 212 ManNLev, ketone-containing, 213 Mannopyranosyl conjugate, 152 D-mannosamines, N-acyl-modified, 213 D-Mannose, 9, 121, 331 Mannose-binding adhesion (FimH), 135 Mannose-decorated liposome, 82 Mannose-specific lectin ConA, 159 ␣-C-Mannoside, 119 Mannosides, pentaerythritol-based, 147 ␣-D-Mannopyranosides, per-O-acetylated, 144 Mannosyltransferases, 340 ␣-(1-6)-Mannosyltransferase, 304 Mass spectrometry, 94 Materials science, 80 Medicinal chemistry, 80 Mefenamic acid (MF), 17 Membrane environment, 79 Membrane-forming capability, 280 Mercuric-assisted cleavage, 25 Mesylates, 246 Metabolic glycoengineering, 213 Metal glyconanoparticles, 167 Metal nanoparticles, alkyne functional (Au), 167 Metal nanoparticles, azide functional (TiO2 ), 167 Metal-free click reaction, photoactivated, 225 Metastatic cancer, 342 Methicilin-resistant Staphylococcus aureus (MRSA), 306 Methionine aminopeptidase II (MetAP2) inhibitor, 346 Methyl 2,3,5-tri-O-acetyl-D-ribofuranoside, 17 Michael addition, 12, 13, 14, 35, 36 Microheterogeneity, 254 Microplate-immobilized liposomes, 86 Micro-tubule stabilizing antitubulin agents, 299 Microwave, activation, irradiation, 145, 193, 197, 257, 258, 261, 338 Minimal hemolytic concentration (MHC), 307 370 INDEX Minimal inhibitory concentration (MIC), 307 Molecular architecture, 152 Molecular brushes, 278 Molecular dynamics (MD), 134 Molecular imaging, metal complexes, 192 Mono-(6-azido-6-deoxy)-␤-CD, 276, 281 Monoglycoside neoglycopeptide, 257 Monohydrothiolation, 46 Monophosphoryl lipid A (MPLA), 91, 338 Monosaccharides, alkynyl containing, 222 Monosaccharides, azide-bearing, 215 Monosaccharides, diazirine crosslinkers, 227 Monosaccharides modified by photoactivatable crosslinking moiety, 227 MUC1 domain, tumor-associated, 259 MUC1 glycoprotein, 259 Mucins, 259 Multimeric ligands, 328 Multivalent glycomaterials, 144 Multivalent glycoside effect, 144 Multivalent heptyl mannosides, 135 Multivalent sialic acid, 307 Multivalent HM ligands, 135, 136 Muscular dystrophies, 254 Musculoskeletal diseases, 288 Mycobacterial ␣-(1,6)mannosyltransferases, 305 Mycobacterium tuberculosis, 304 Myristoylation, 100 Nanoprecipitation, 161 Naphthylmethyl (NAP) group, 23 Native chemical ligation (NCL), 254, 255, 262, 263, 264, 267 NBD label, 82 Neoglycoconjugates, 122, 338, 351, 354 Neoglycopeotide mimics, 259 Neoglycopeptide, 9, 11, 255, 257, 259, 264 Neoglycopeptide, penta-clicked, 261 Neoglycopeptides, triazole-linked, 256 Neoglycopolymer, 5, 157, 161 Neoglycopolymer–BSA conjugates, 157 Neoglycopolymer–protein hybrid materials, 157 Neoglycoproteins, 255, 257, 262, 265 Neoglycoprotein constructs, de novo synthesis, 264 Neoglycosyl amino acid building blocks, 257 Neomycin B, 306 Neuraminic acid (NANA), 348 Neuraminic acid ligands, 150 Neuraminic acid mimic zanamivir, 173 Neuraminic acids, N-acyl-modified, 213 Neuraminidase, 348, 349 Neuraminidase inhibitors, 115 Neuraminidase inhibitory activity, 309 Neuroendocrine tumors, 200 Neuronal differentiation, 228 Noncovalently connected micelles (NCCMs), 287 Neurotensin (NT), 189 Neurotensin receptor (NTR-1), peptidic ligand of, 189 Neurotensin-based radiotracers, 202 Neurotransmitter, 202 Nitrile oxide, 226 Nitroimidazole, 204 N-methylhydroxylamine, 226 Nonapeptide, Thr-Ala-Leu-Asn-Cys-Asn-Asp-SerLeu, 68 Nondeleterious effect of glycosylation, 192 Nonspecific protein labeling, 97 NT (tridecapeptide), 202 NT-based radiotracers, 202 NTR1 receptors, 202 Nuclear imaging techniques, 183 Nuclear medicine, 184 Octahydrosilsesquioxane, 169 Octapeptides, Asp-Leu-Tyr-Cys-Tyr-Glu-Gln-Leu, 66 Octavalent S-glucoside cluster, 53 Octavalent glycoclusters, 149 Octavinyl POSS, 55 Octreotide, 200, 201 carbohydration, 200 Lys0 Tyr3, 201 Octyl-␤-glucopyranoside, 86 (1,6)-Oligomannose analogs, 304 Oligomannose cluster, 151 Oligonucleotide, carbohydrate-centered glycocluster, 152 INDEX Oligonucleotide-based probes, 197 Oligorotaxanes, 123, 279 Oligosaccharide antigens, 298 Oligosaccharide transferase complex, 212 Oligosaccharides, N-linked, 211 Oligosilsesquioxanes, 55 Organic–inorganic hybrid materials, 55 Orthogonality, 54 Oseltamivir, 349 Osteoblasts, 288 Osteoclasts, 288 Osteocytes, 288 Osteotropicity, 289 1,2,4-Oxadizole, 298 Oxazolines, 226 Oxidative stress, 100 Oxime ligation, alanine mediated, 214 Oxime-forming reactions, 152 Oxyluciferin, bioluminescent, 220 Paclitaxel, 299 Palmitoyl groups, 98 Palmitoylation, 100 Pancreatic carcinoma cells, 202 PEG-linked octaene silsesquioxane, 57 Pendimethalin, 282 Pentaalkynyl C60 fullerene, 165 Pentacosa-10,12-diynoic acid (PCDA), 161 Pentaethylenehexamine, Boc-protected, 164 2-O-Pentafluoropropionyl acetobromomannose, 188 Pent-4-enofuranoside, 48 4-Pentynoyl mannosamine Ac4ManNAl, 216 Peptide, 62 Peptide, [18 F]FDG-containing, 203 Peptide glycoconjugates, 191 Peptide, glycosylated, 202 Peptide, RGD-containing, 203, 206 Peptides, secondary and tertiary structures, 253 Peptide labeling, use of carbohydrates for, 188 Peptide receptor, gastrin-releasing, 202 Peptide scaffold, 254 Peptide-azide, ligation, 260 Peptide–oligonucleotide conjugates, triazole-linked, 260 Peptide-thioester, 264 371 Peptidomimetic chemistry, 256 ␤-Peptoids, 146 Peptoids, alkynyl-substituted, 260 Peracetylated D-mannopyranose, 38 Peracetylated ␤-monosaccharides, 17 Peracetylated 1-thio-␤-D-glucose, 48 Pharmacokinetics, 188, 199, 206 Phe-Gly-Trp-Cys-Tyr-Lys-Leu-Val, 66 Phenyl azide, 97 Phenylalanine, ethyl ester, 63 ␣-Phenylethyl-ammonium chloride, 240 (R)-(-)-2-Phenylglycine (␤-cyclodextrin, ␤-CD), 148 Phenylthiosulfonate, 205 Phos–Flag, 218, 219 Phosphate headgroup, 94 Phosphatidic acid (PA), 88 Phosphatidylcholine (PC), 82 Phosphatidylethanolamine (PE) analog, 82 Phosphatidylglycerol (PG), 82 Phosphatidylinositol polyphosphates (PIPn s), 98 Phosphatidylinositol-(4,5)-bisphosphate (PI-(4,5)P2), 98 Phosphine–luciferin conjugate, 220 Phosphodiester oligomers, 146 Phosphoglycopeptide, 24 Phospholipase D hydrolysis, 95 Phospholipase, 94, 97 Phosphoramidite, alkyne-armed, 152 Phosphoramidites, 197 Photoactivatable crosslinking sugars, 227 Photoaddition of thiols, 121 Photoaddition, 46 Photoaffinity tag, 88, 95 Photochemically triggered click reaction, 225 Photo-cross-linking, 95 Photoinduced coupling, 11 Photo-initiated copolymerization, 276 Photoinitiator, 14 Pk trisaccharide moiety, 165 PKC isoforms, 88 PKC␣ binding, 88 Plant lectin ConA, 156 Plasmid DNA (pDNA), 164 Poly(p-phenylethynylene), 162 Poly(propargyl methacrylate), 157 Poly[p-(azidomethyl)]styrene, 160 372 INDEX Polyamidoamine polycationic scaffolds, 164 Polyanionic carbohydrate ligands, 334 Polyazide glycopolymer, 161 Polycationic ␤-CD, 283 Polycationic nanoparticles, 284 Polycytosine (polyC), 161 Polyethylene glycol (PEG), 277 Polyfluorenes with pendant sugars, fluorescent conjugated, 162 Polyglycerol, hyperbranched, 159 Polyhedral oligosilsesquioxanes (POSS), 55 Polymeric prodrug, 289 Polymeric scaffolds, 131 Polymerization, 11, 14 Polymerization initiator, benzyl ␣-bromoester, 155 Polymerization of functional glycomonomers, 154 Polypeptides, 146 Polypeptide GalNAc transferases, 216 Polyphosphazene click glycopolymers, 159 Polyrotaxane (PR), 148, 277, 289 Polysaccharide, 5, Porcine liver esterase (PLE), 17 Porphyrins, 9, 10, 151 Positron emitter tomography (PET), 184 Positron emitters, 187 POSS-based glycoconjugate, 55 Post-glycosylation, 154 Post-translational, 253 Post-translational modification, 155, 211 Post-translational S-palmitoylation of cysteine, 98 Pre-biosynthesized proteins, 155 Primary silyl ethers deprotection, 26 Probe–protein conjugation, 95 Proliferation imaging agent, 196 N-propargylamidomethyl-␤-Dglucopyranoside, 161 S-propargylcysteine, 191 Propargyl amino acid, 188 Propargyl bromide, 333 Propargyl ethers, 19, 21 Propargyl ␤-D-galactopyranoside, 128, 148 S-propargyl glutathione, 66 Propargyl glycosides, 109 Propargyl group, disarmed, 193 Propargyl methacrylate (PMA), 280 Propargyl sugar, 257, 262 Propargylamine, 277 Propargylated glutathione, 190 Propargylated peptides, 259, 261 Propargyl–choline, 94 Propargyl–glycine, 192, 195, 258, 266 L-propargyl-glycine, 189 Propargyl-␤-lactam, 331 Propargyloxycarbonyl (Poc) group, 26, 28 Propylthio ␣-D-C-glucopyranoside, 56 Prostaglandins E2, 289 Prosthetic group, 185, 206 Protease, 253 N-protected allyl glycinate, 62 N-protected glucosyl amino acid, 63 N-protected vinyl glycinate, 62 Protein, 62 Protein apocytochrome c, 97 Protein glycosylation, 211 Protein kinase C(PKC)␣, 86 Protein lipidation, 98, 99 Protein prenylation, 100 Protein receptor, 151 Protein receptors (lectins), 143 Protein, 62 Protein-carbohydrate interactions, 52 Protein-lipid-binding, 81, 95 Protein–membrane binding, 79, 85, 86 Protein–membrane-binding interactions, 85 Proteins, extracellular, 253 Proteins, O-GlcNAc-modified, 216 Proteins, membrane, 253 Protein-SH conjugation, 158 Proteoglycans, 143 Prothrombin-1, 98 Pseudodisaccharide pendant units, 161 Pseudo-glycoconjugates, 115 Pseudomonas aeruginosa, 149, 166 Pseudooligosaccharides, 343 Pseudorotaxanes, 148 Pseudopolyrotaxanes, 278 Pyridine derivatives, as metal chelators, 193 Pyridinyl prosthetic groups, 199 Q␤ bacteriophage capsid particles, 169 Q␤-(Hag16) protein, 64 Quartz crystal microbalance (QCM), 171 Quaternary ammonium salts, 240 INDEX Radical homocoupling of thiol, 46 Radiochemistry, 206 Radioelements, gamma-emitting, 184 Radioisotopes, 184, 315 Radioligand, 202 Radiometal chelate, di-triazolyl, 193 Radiometals, in PET, 192 Radiometals, in SPECT, 192 Radiotracers, 184, 200, 201, 202, 206 Ras superfamily, 98 Reductive cleavage, 12 Resorcin[4]arene derivatives, 151 Resorcinarenes (resorcarenes), 148 Retro-Diels–Alder reaction, 157 Reversible addition-fragmentation chain transfer (RAFT) polymerization, 161 RGD peptide, 85 Rheumatoid arthritis, 254, 330 Rhodamine, 278 Rhodamine B derivative, fluorescent, 157 RKO cell lines, 100 RNAs, small interfering (siRNA), 199 Roscovitine, 298 Rotaxanation, 148 Saccharides, amino acids-containing, 223 Saccharides, azido-containing, 223 Sacrificial unit, 4, 5, Samarium, 19, 21 Scaffolds, bifunctional, 145 Scaffolds, clickable, 146 Self-assembled monolayer (SAM), 171 Scaffold, 286, 315, 333 L-Selectin, 330 Selectin antagonists, 303 Selectins, 329 SEQUEST, 222 Serine hydrolases, 97 Serine, direct glycosylation of, 204 Shiga-like toxins, 130, 166 29 Si NMR spectroscopy, 59 5-SiaDAz, peracetylated, 228 Sialic acid, 52, 149, 238, 314 ␣-Sialic acid azide, 113 Sialic acid biosynthetic enzymes, 216 Sialic acid biosynthetic pathway, promiscuous, 213 Sialic acid derrivatives, 128 sialic acid residues, alkyne-armed, 169 373 sialic acid, modified with a photo-activated Sialic acid-containing glycans, 215 Sialic acids, selective oxidation, 214 Sialic thiols, 58 Sialoclusters, 56 Sialoconjugation, 56 Sialyl N-acetyllactosamine, 303 Sialylated glycans, alkyne-modified, 220 Sialylated N-linked glycoproteins, 222 SialylLewisa (sLea ), 303 SialylLewisx (sLex ), 303, 331 Sialyltransferases, 213 Silvestrol, 298 Silica surface, ligation of carbohydrates, 169 Silica-supported sodium hydrogen sulfate, 24, 26 Silicon wafer chips, azide-functionalized, 171 Silsesquioxane-based glycoclusters, 55 Silsesquioxane-based octavalent glycocluster, 58 Silyl group, hydrolysis, 193 Silylating agent, 246 Silylation, 243 Site-selective protein modification (hyperglycosylation), 70 SN2-type substitution, 34 Sodium ascorbate, 110, 125 Solid phase synthesis (SPS), 334 Solid-phase peptide synthesis (SPPS), 254, 255, 262, 267 Somatostatin receptor (SST)-positive tumors, imaging of, 201 Somatostatin receptor ligands, 200 SPAAC, 222 Sphingomyelinase, 94 Splenocytes, 219 SPR assays, 88 SPR, 166, 171 SPR-based competitive assay, 159 Staphylococcus aureus, 307 Starch, Staudinger ligation, 80, 81, 85, 100, 217, 219 Steric congestion, 56 Steric effects, 51 Steric factors, 244 Stimulation of monocytes, 148 374 INDEX Strain-promoted azide–alkyne cycloaddition (SPAAC), 46, 71 Strain-promoted cycloaddition, 81, 226 Succinimidyl 5-azido valerate, 199 Sucrose (␤-D-fructofuranosyl ␣-D-glucopyranoside), 239 Sucrose azide, 246 Sucrose azidoacetylene, 243 Sucrose “click” receptors, 249 Sucrose macrocycles, 235, 246 Sucrose macrocycles, fully benzylated, 248 Sucrose scaffold, 239, 240 Sucroses, C2-symmetrical, 247 Sucroses, cyclization of, 248 Sugar azide, 113 Sugar azide, labeled, 188 Sugar-binding proteins, 52 Sugars, acetylene armed, 159 Sugars, thiol containing, 228 Supported lipid bilayers (SLBs), 83 Supramolecular chemistry, 80 Supramolecular polymer, 278 Surface plasmon resonance (SPR) assay, 88 Surface plasmon resonance (SPR)–binding, 157 Surfactant micelles, alkynylated, 162 Surfactants, 239 Sweet almond glucosidase (SAG), 310, 342 Talaromyces flavus CCF 2686, 298 Tc(CO)3 chelator, 202 T Cell receptor, 298 N-terminal phenylalanine of Lys5 (Boc)Tyr3 -2,3,4,6-Tetra-O-acetyl-␤-Dglucopyranosyl azide, 298 Tetraalkynyl porphyrine scaffold, 167 Tetra-allyl calix[4]arene, 52 Tetrabenzo[a,c,g,i]fluorene, azide-armed, 167 N-tetradecyl propargylamide, 171 Tetraethylene glycol spacer, 81 Tetralactosyl click clusters, calix[4]arene-centered, 149 Tetrapeptide RGDC (Arg-Gly-Asp-Cys), 10, 66, 190 Tetrathiomolybdate, 26, 36 1,3,4,6-Tetra-O-acetyl-2-azido-2-deoxy-Dgalactose, 257 99m Tetra-O-acetyl-2-deoxy-2-fluoro-glucose, cold, 204 2,3,4,6-Tetra-O-acetyl-glucosyl amine, 191 Tetraubiquitin protein, 262 Tetrasaccharide [Man␣1,2Man␣1, 2Man␣1,3Man␣], azide-armed, 151 Tetravalent glycoclusters, 149 Tetravalent, 52 Tf receptors, 169 Thermomyces lanuginose, 17 Thermoresponsive micelles, 11 Thermosensitive polymer, 279 Thiazolidine (Thz), 263 Thioacetates, 50 ␥ -Thiobutyramides, 55 1-Thio-␤-D-glucose, 55, 58 1-Thio-␤-D-lactose, 61 1-Thio-␤-D-mannose, 61 1-Thio-␤-mannopyranoside, 38 Thioacetic acid, 50 Thio-conjugation, 33 Thiodisaccharide, 11, 34, 35, 36 Thioglucoside, 13 Thioglycoside, 12 Thiol 1,4-addition, on the succinimide moiety, 203 Thiol Michael enone addition (TMEA), 34, 35, 37 Thiolate, 12 Thiolates, propargylamido-terminated, 171 Thiol-ene coupling/chemistry (TEC), 10, 14, 33, 36, 37, 46, 60 Thiols (addition) to multiple bonds, Thiol-yne coupling/chemistry/addition (TYC), 14, 33, 37, 46 1-Thio-␤-D-galactosides, 312 ␣-Thiomannose-azide conjugate, 82 Thioethers, 121 Thiopropargyl glycosides, 109 Thiosugar, 12, 200 Thiourea, 121 Thiourea-forming reactions, 152 Thioxylooligosaccharides, 39 Thiram, 282 Thiyl radical, 50 Thr8 octreotide analog, amino group of, 201 Threonine, direct glycosylation of, 204 Thymidine kinase-1 (TK1), 196 Thymidine, -azido, 192 INDEX Thymidine, -azido, 197 Thymidine, labeled at N-3 position, 194 Thymidine, -triazolo, 198 Thymidine, -triazolo, 198 Thymidyl-triazolo-alanine, 193 Thz-neoglycopeptide, 263 Tissue engineering, 164, 228 TLC-based assay, 94 T-Lymphocytes, 334 p-Toluenesulfonic acid, 20 Tomography (SPECT), 184 Tosylhexenose, unsaturated, 35 Transferrin (Tf), glycan chain, 169 ␣,␣ -Trehalose derivative, 145, 146 Triarylphosphine-TAG conjugates, 219 Triazidated ␣-CD, 278 -Triazol-N-acetyllactosamine(LacNAc), 327 3-Triazol-galactosides, 327 1,2,3-Triazole, 108, 296, 306, 309, 318 1,2,3,-Triazole scaffold, 326 1,2,3-Triazole linkage, 256 1,2,3-Triazole ring, 109, 111, 115, 132 Triazole ring, anomeric, 157 Triazole-containing radiotracers, 186 Triazole-linked C-glycocluster, 4, 54 1,2,3-Triazole-sialic acid, 351 Triazoles, regioisomeric, 244 Triazolyl galactoside, 301 Triazolyl-glucose, 197 Triazolyl-thymidine, 197 Triazolyl-thymidine, 18 F labeled, 196 2-O-Triflate mannopyranose, 187 2-O-Triflyl-manno derivatives fluorination at C-2, 189 Trimethylsilyl (TMS)-protected, 155 Trimethylsilyl triflate, (TMSOTf), 38, 40 Tripanocidal activity, 149 Tripeptide, 65 Tris-(2-carboxyethyl)phosphine (TCEP), 100, 261, 262, 263 Tris-(TEG-triazole)-based ligand, 84 Tris-(triazolyl)benzylamine (TBTA), 199 Tris[1-benzyl-1H-1,2,3-triazol-4ylmethyl]amine (TBTA), 220 Tris-3-hydroxypropyltriazolylmethylamine (THPTA), 220 Trityl group deprotection, 24, 26 375 Trivalent lactoside, 303 Trypanosoma cruzi trans sialidase (TcTS), 128, 298, 300, 351 Tumor cell proliferation, probe for, 196 Tumor metastasis, 107, 129, 143 Tumor-associated carbohydrate antigens, 334 Tumor-associated glycoprotein, 334 Tumor proliferation, enzyme, 195 Turbidimetry, 156 Tyrocidine (Tyc), 306 Tyrosine residue, standard iodination with 125 I, 192 UDP-GalNAz, 216 UDP-GlcNAc 2-epimerase, lack of, 228 UDP-GlcNAz, 216 Ulex Europaeus Lectin (UEL-1), 331, 333 Ultrasonic imaging, 183 Ultrasonication, 95 Ultrasound, 4, 54 Unilamellar vesicles, 161 Unsymmetrical dendrimers, 316 Uridine diphospho UDPGalNAz, 216 Valienamine, 343 Vancomycin-resistant Enterococci (VRE), 306 Vesicle, 79 Viral envelope glycoprotein gp120, 158 Viral infection, 309 Viral neuraminidase, inhibitor, 173 Virus, BK, 149 Virus, influenza A, 149 Virus-like nanoparticle, 64 Vitronectin receptor, 191 Western blotting, 222, 228 X-ray examination, 183 Yeast ␣-mannosidase, 173, 174 Zanamvir analogs, 348 Zeolites, Cu(I)-modified, 236 Zinc(II), Zirconium chloride, 25 Click Chemistry in Glycoscience: New Developments and Strategies, First Edition Edited by Zbigniew J Witczak and Roman Bielski © 2013 John Wiley & Sons, Inc Published 2013 by John Wiley & Sons, Inc S S 28a-c O O P O O c: R1 = O, R2 = b: R1 = H2, R2 = a: R1 = O, R2 = O O O O R2 O O R1 N 30 O O O P O 29 N Cell membrane O O O C13H27 C13H27 O Biosynthetic Incorporation OH N3 Bioorthogonal labeling O N O N N N NH3 N 32 O O P O 31 O O P O 33 O P O O O O O O HN O O O O 14 C15H31 C13H27 O C13H27 O C13H27 OH O O FIGURE 4.8 Strategies for in situ labeling of tagged lipid analogs (a) Cartoon depicting bioorthogonal labeling of lipids in complex environment (b) Structures that have been developed for in situ labeling studies (b) (a) b: R1 = a: R1 = N O O O O 34a-b O N3 10 N3 10 N3 N 35b O P O O O 35a O O P O O O O O 15 16 15 16 F P O O O O NH3 O O P O and enrichment Protein labeling O F P O N3 O P O O N Lipid-binding Protein 36 O O O 14 O O O NH O Lipid-binding Protein N N O O3PO -2 O3PO -2 N OH OH O O P O O OH 37 6N H O Protein Identification H N N3 O O FIGURE 4.9 The development of activity-based lipid probes (a) Cartoon depicting the application of lipid activity probes for the labeling and identification of target proteins (b) Examples of lipid activity probes that have been reported R (b) (a) (a) O O P O O O P O O Cell extract incubation Protein Purification / Detection N3 N3 Labeled lipidated protein Tagged lipid substrate (b) O O O P O P O O O N3 38 O R SCoA 41a-b a: R = N3 N3 b: R = OH 39 O O R R OH H OH 40a-b 42a-b a: R = N3 a: R = (CH2)2N3 b: R = b: R = FIGURE 4.10 Investigation of covalent protein lipidation using bioorthogonal labeling (a) Cartoon depicting the covalent labeling of target using azide-tagged lipid substrate analogs (b) Examples of structures used to infiltrate covalent protein modification using tagged lipid substrate derivatives O NH HO HO HO O N O O OH HO 18F [18F]FDG FIGURE 7.1 18F [18F]FLT Two labeled carbohydrates used in PET Covalent bonding Complexation Direct labeling Y a Metal chelating group c Biomolecule Y Y Y d PG X b Prosthetic group Y PG Y FIGURE 7.2 Strategies for the construction of radiotracers Bone Osteotropic molecular host FIGURE 11.1 sequestrant Soft tissues Bone anabolic agent Guest/host molecular complex The proposed bone anabolic mechanism of ALN-␤-CD as a molecular 10 x106 (a) (b) FIGURE 11.2 The early identification of breast cancer bone metastasis lesion by NIR dyelabeled osteotropic polyrotaxane (a) Luciferase activity associated with breast cancer cells was mainly found at knee joints (bone metastatic sites) and heart (due to intracardial injection of Luciferase-expressing breast cancer cells); (b) High signal intensity of NIR-dye-labeled osteotropic polyrotaxane was found at knee joints but not the heart, which identifies these positions as cancer bone metastasis ... thiol-yne coupling tyrocidine ultraviolet vancomycin resistant enterococci PART I CLICK CHEMISTRY STRATEGIES AND DECOUPLING Click Chemistry in Glycoscience: New Developments and Strategies, First... categories: Click chemistry strategies Thio -click chemistry of carbohydrates Click chemistry related to life science and glycobiology Click chemistry related to medicinal chemistry The introductory... xvii I CLICK CHEMISTRY STRATEGIES AND DECOUPLING Paradigm and Advantage of Carbohydrate Click Chemistry Strategy for Future Decoupling Roman Bielski and Zbigniew J Witczak II THIO -CLICK CHEMISTRY