Carbohydrate-based Drug Discovery, 2 Volume Set

Professor Chi-Huey Wong received his B.S. and M.S. degrees from National Taiwan University, and Ph.D. in Chemistry (with George Whitesides) from Massachusetts Institute of Technology in 1982. He started his independent career as Assistant Professor of Chemistry at Texas A&M University in 1983, where he became Full Professor in 1987. He has been Professor and Ernest W. Hahn Chair in Chemistry at the Scripps Research Institute since 1989 and is also a member of the Skaggs Institute for Chemical Biology since 1996.Professor Wong is a member of the U.S. National Academy of Sciences and the American Academy of Arts and Sciences. He is a recipient of The Searle Scholar Award in Biomedical Sciences (1985), the Presidential Young Investigator Award in Chemistry (1986), the American Chemical Society A.C. Cope Scholar Award (1993), the Roy Whistler Award of the International Carbohydrate Organization (1994), the American Chemical Society Harrison Howe Award in Chemistry (1998) and the Claude S. Hudson Award in Carbohydrate Chemistry (1999), the International Enzyme Engineering Award (1999) and the Presidential Green Chemistry Challenge Award (2000). He is a member of Academia Sinica, Taipei (1994), the American Academy of Arts and Sciences (1996) and the US National Academy of Sciences (2002). He serves as editor-in-chief of Bioorganic and Medicinal Chemistry and is an executive board member of the Tetrahedron Publications. He was head of the Frontier Research Program on Glycotechnology at RIKEN (Institute of Physical and Chemical Research, Japan) (1991-1999) and is currently a scientific advisor of the Max-Planck Institute, a board member of the U.S. National Research Council on Chemical Sciences and Technology, and is a founding scientist of Optimer Pharmaceuticals, Inc. He is author and co-author of over 450 publications, 60 patents and several books.His current interests are in the areas of bioorganic and synthetic chemistry and biocatalysis, including development of new synthetic chemistry based on enzymatic and chemo-enzymatic reactions, synthetic approach to carbohydrate-mediated biological recognition, design and synthesis of mechanism-based inhibitors of enzymes, RNA and carbohydrate receptors, development of oligosaccharide and aminoglycoside microarrays for high-throughput screening and the study of reaction mechanisms.

• Volume 1Preface xxvList of Contributors xxvii1 Synthetic Methodologies 1Chikako Saotome and Osamu Kanie1.1 Introduction 11.2 Tactical Analysis for Overall Synthetic Efficiency 11.3 Methodological Improvements 21.4 Accessibility 111.5 Concluding Remarks 321.6 References 332 Complex Carbohydrate Synthesis 37Makoto Kiso, Hideharu Ishida, and Hiromune Ando2.1 Introduction 372.2 Synthetic Gangliosides 382.3 Toxin Receptor 502.4 Summary and Perspectives 522.5 References 523 The Chemistry of Sialic Acid 55Geert-Jan Boons and Alexei V. Demchenko3.1 Introduction 553.2 Chemical and Enzymatic Synthesis of Sialic Acids 563.3 Chemical Glycosidation of Sialic Acids 593.4 Enzymatic Glycosidations of Sialic Acids 833.5 Synthesis of C- and S-Glycosides of Sialic Acid 913.6 Modifications at N-5 943.7 References 954 Solid-Phase Oligosaccharide Synthesis 103Peter H. Seeberger4.1 Introduction 1034.2 Pioneering Efforts in Solid-Phase Oligosaccharide Synthesis 1044.3 Synthetic Strategies 1054.4 Support Materials 1074.5 Linkers 1084.6 Synthesis of Oligosaccharides on Solid Support by Use of Different Glycosylating Agents 1124.7 Automated Solid-Phase Oligosaccharide Synthesis 1184.8 Conclusion and Outlook 1244.9 References 1255 Solution and Polymer-Supported Synthesis of Carbohydrates 129Shin-Ichiro Nishimura5.1 Introduction 1295.2 Mimicking Glycoprotein Biosynthetic Systems 1305.3 References 1366 Enzymatic Synthesis of OligosaccharidesJianbo Zhang, Jun Shao, Prezemk Kowal, and Peng George Wang6.1 Introduction 1376.2 Sugar Nucleotide Biosynthetic Pathways 1406.3 Enzymatic Oligosaccharide Synthesis Processes 1516.4 Future Directions 1626.5 References 1627 Glycopeptides and Glycoproteins: Synthetic Chemistry and Biology 169Oliver Seitz7.1 Introduction 1697.2 The Glycosidic Linkage 1697.3 The Challenges of Glycopeptide Synthesis 1717.4 Synthesis of Preformed Glycosyl Amino Acids 1737.5 Synthesis of Glycopeptides 1817.6 Biological and Biophysical Studies 2007.7 Summary and Outlook 2087.8 References 2098 Synthesis of Complex Carbohydrates: Everninomicin 13,384-1 215K. C. Nicolaou, Helen J. Mitchell, and Scott A. Snyder8.1 Introduction 2158.2 Retrosynthetic Analysis and Strategy 2188.3 Total Synthesis of Everninomicin 13,384-1 (1) 2238.4 Conclusion 2498.5 References 2509 Chemical Synthesis of Asparagine-Linked Glycoprotein Oligosaccharides: Recent Examples 253Yukishige Ito and Ichiro Matsuo9.1 Introduction 2539.2 Synthesis of Asn-Linked Oligosaccharides: Basic Principles 2579.3 Chemical Synthesis of Complex Oligosaccharides 2619.4 References 27810 Chemistry and Biochemistry of Asparagine-Linked Protein Glycosylation 281Barbara Imperiali and Vincent W.-F. Tai10.1 Protein Glycosylation 28110.2 Small-Molecule Probes of the Biochemistry of Oligosaccharyl Transferase 28310.3 Conclusions 30110.4 References 30111 Conformational Analysis of C-Glycosides and Related Compounds: Programming Conformational Profiles of C- and O-Glycosides 305Peter G. Goekjian, Alexander Wei, and Yoshito Kishi11.1 Introduction 30511.2 Stereoelectronic Effects and te exo-Anomeric Conformation 30611.3 Conformational Analysis of C-Glycosides: C-Monoglycosides 30911.4 1,4-Linked C-Disaccharides: the Importance of syn-Pentane Interactions 31411.5 Prediction of Conformational Preference and Experimental Validation 31811.6 Programming Oligosaccharide Conformation 32211.7 Conformational Design of C-Trisaccharides based on a Human Blood Group Antigen 32311.8 Conformational Design: Relationship to Biological Activity 33011.9 Concluding Remarks 33611.10 Acknowledgements 33711.11 References 33712 Synthetic Lipid A Antagonists for Sepsis Treatment 341William J. Christ, Lynn D. Hawkins, Michael D. Lewis, and Yoshito Kishi12.1 Background 34112.2 Hypothesis and Approach 34212.3 Conclusion 35112.4 Acknowledgement 35312.5 References 35313 Polysialic Acid Vaccines 357Harold J. Jennings13.1 Introduction 35713.2 Group C Meningococcal Vaccines 35813.3 Group B Meningococcal Vaccines 36213.4 Chemically Modified Group B Meningococcal Vaccines 36613.5 Cancer Vaccines 37113.6 Acknowledgements 37513.7 References 37514 Synthetic Carbohydrate-Based Vaccines 381Stacy J. Keding and Samuel J. Danishefsky14.1 Introduction 38114.2 Cancer Vaccines 38214.3 Bacterial Polysaccharide Vaccines 39714.4 Synthetic Parasitic Polysaccharide Conjugate Vaccine 40214.5 Conclusions 40314.6 References 40315 Chemistry, Biochemistry, and Pharmaceutical Potentials of Glycosaminoglycans and Related Saccharides 407Tasneem Islam and Robert J. Linhardt15.1 Introduction 40715.2 Dermatan and Chondroitin Sulfates 41715.3 Hyaluronan 41915.4 Keratan Sulfate 42315.5 Other Acidic Polysaccharides 42515.6 Pharmaceutical Potential and Challenges 43015.7 Conclusion 43215.8 References 43316 A New Generation of Antithrombotics Based on Synthetic Oligosaccharides 441Maurice Petitou and Jean-Marc Herbert16.1 Introduction 44116.2 Heparin and Its Mechanism of Action as an Antithrombotic Agent 44216.3 Synthetic Pentasaccharides, Selective Factor Xa Inhibitors, are Antithrombotic Agents 44616.4 Synthetic Thrombin-Inhibiting Oligosaccharides: The Next Generation? 45216.5 The Mechanism of Antithrombin Activation by Synthetic Oligosaccharides 45616.6 Conclusion and Perspectives 45616.7 References 457Volume 217 Sequencing of Oligosaccharides and Glycoproteins 461Stuart M. Haslam, Kay-Hooi Khoo, and Anne Dell17.1 Mass Spectrometry 46217.2 MS-Based Sequencing Strategies 46617.3 Glycan Sequencing and Structural Determination – A Case Study 47017.4 Mammalian Glycomics 47517.5 Some Special Case Strategies 47717.6 References 48118 Preparation of Heterocyclic 2-Deoxystreptamine Aminoglycoside Analogues and Characterization of their Interaction with RNAs by Use of Electrospray Ionization Mass Spectrometry 483Richard H. Griffey, Steven A. Hofstadler, and Eric E. Swayze18.1 Introduction 48318.2 ESI-MS for Characterization of Aminoglycoside-RNA Interactions 48418.3 Preparation of Heterocyclic 2-Deoxystreptamines and Binding to a 16S A Site RNA Model 49018.4 Preparation, Binding, and Biological Activity of Substituted Paromomycin Derivatives 49518.5 Future Prospects 49818.6 Acknowledgements 49818.7 References 49819 Glycosylation Analysis of a Recombinant P-Selectin Antagonist by High-pH Anion-Exchange Chromatography with Pulsed Electrochemical Detection (HPAEC/PED) 501Mark R. Hardy and Richard J. Cornell19.1 Introduction 50119.2 Use of HPAEC/PED in the Development of Biopharmaceuticals 50219.3 Biology of P-Selectin 50319.4 HPAEC/PED as an Adjunct to rPSGL-Ig Process Development 50419.5 Results and Discussion 50819.6 Summary 51519.7 Acknowledgements 51619.8 References 51620 Analytical Techniques for the Characterization and Sequencing of Glycosaminoglycans 517Ram Sasisekharan, Zachary Shriver, Mallik Sundaram, and Ganesh Venkataraman20.1 Introduction to GAG Linear Complex Polysaccharides 51720.2 Depolymerization of Nascent GAG Chains 52120.4 Analytical Tools Used in the Structural Characterization of GAGs 52720.5 Future Directions 53620.6 Acknowledgements 53720.7 References 53721 Thermodynamic Models of the Multivalency Effect 541Pavel I. Kitov and David R. Bundle21.1 Introduction 54121.2 Concept of Distribution Free Energy 54221.3 Multivalent Receptor vs. Monovalent Ligand 54621.4 Multivalent Receptor vs. Multivalent Ligand 55121.5 Topological Classification of Multivalent Systems 55321.6 Determination of Microscopic Binding Parameters by Molecular Modeling 55521.7 Determination of Microscopic Binding Parameters from Binding Data 56121.8 Thermodynamic Analysis of Multivalent Interaction 56221.9 Conclusions 57021.10 Mathematical Appendix 57021.10.1 Calculation of Statistical Coefficients 57021.10.2 Multivalent Receptor and Monovalent Ligand 57121.10.3 Multivalent Binding with Linear and Circular Topology 57121.10.4 Multivalent Binding with Radial Topology 57221.10.5 Derivation of Eq. (24) 57221.11 References 57322 Synthetic Multivalent Carbohydrate Ligands as Effectors or Inhibitors of Biological Processes 575Laura L. Kiessling, Jason K. Pontrello, and Michael C. Schuster22.1 Introduction 57522.2 Multivalent Carbohydrate Ligands as Inhibitors 58122.3 Multivalent Carbohydrate Ligands as Effectors 59622.4 Conclusions 60522.5 References 60523 Glycosyltransferase Inhibitors 609Karl-Heinz Jung and Richard R. Schmidt23.1 Introduction 60923.2 Glycosyltransferases Utilizing NDP-Sugar Donors 61023.3 Glycosyltransferases Utilizing NMP-Sugar Donors 64123.4 Bisubstrate Analogues as Inhibitors 64823.5 Conclusion 65323.6 References 65424 RNA-Aminoglycoside Interactions 661Haim Weizman and Yitzhak Tor24.1 RNA as an Emerging Therapeutic Target 66124.2 Aminoglycoside Antibiotics: Past and Present 66424.3 Aminoglycosides as RNA Binders 66624.4 Identifying RNA Targets and Developing Binding Assays 67024.5 Dimeric Aminoglycosides 67324.6 Aminoglycoside-Intercalator Conjugates 67524.7 Guanidinoglycosides 67724.8 Summary and Outlook 67924.9 Acknowledgements 68024.10 References 68025 Glycosylated Natural Products 685Jon S. Thorson and Thomas Vogt25.1 Introduction 68525.2 A Summary of Bioactive Glycosylated Secondary Metabolites 68625.3 Conclusions 70725.4 References 70726 Novel Enzymatic Mechanisms in the Biosynthesis of Unusual Sugars 713Alexander Wong, Xuemei He, and Hung-Wen Liu26.1 Introduction 71326.2 Biosynthesis of Deoxysugars 71426.3 Biosynthesis of Aminosugars 72526.4 Biosynthesis of Branched-Chain Sugars 73026.5 Epimerization Reactions 73426.6 Rearrangement of Hexose Skeletons: UDP-Galactopyranose Mutase-Catalyzed Biosynthesis of Galactofuranose 73826.7 Summary 74026.8 Acknowledgements 74126.9 References 74127 Neoglycolipids: Identification of Functional Carbohydrate Epitopes 747Ten Feizi, Alexander M. Lawson, and Wengang Chai27.1 Rationale for Developing Neoglycolipids as Oligosaccharide Probes 74727.2 The First and Second Generation Neoglycolipids 74927.3 Mass Spectrometry of Neoglycolipids 75027.4 Scope of the Neoglycolipid Technology 75227.5 Oligosaccharide Microarrays 75527.6 Summary and Perspectives 75727.7 Acknowledgement 75727.8 References 75728 A Preamble to Aglycone Reconstruction for Membrane-Presented Glycolipid Mimics 761Murugesapillai Mylvaganam and Clifford A. Lingwood28.1 Introduction 76128.2 The Role of Ceramide Subtype Composition 76228.3 Effects of Ceramide Subtype Composition in the Binding of Gb3Cer to Verotoxins 76428.4 Hypothesis Regarding Lipid Replacement Structural Motifs (LRSMs) 76628.5 Effect of Replacement of GSL Fatty Acyl Chains with Rigid, Non-Planar Hydrophobic Groups 76828.6 Ada-Gb3Cer, a Functional Mimic of Membrane Presented Gb3Cer for VT Binding 76928.7 Ceramide Subtype-Dependent Binding of Heat Shock Protein Hsp70 to Sulfogalactosyl Ceramide 77228.8 Adamantyl-Acyl Ceramide is a Functional Replacement for a Ceramide-Cholesterol Composition: A Study with HIV Coat Protein gp120 77528.9 Acknowledgement 77728.10 References 77729 Small Molecule Inhibitors of the Sulfotransferases 781Dawn E. Verdugo, Lars C. Pedersen, and Carolyn R. Bertozzi29.1 Introduction: Sulfotransferases and the Biology of Sulfation 78129.2 EST as a Model ST for Inhibitor Design 78329.3 Inhibition of Representative Golgi-Resident Sulfotransferases: GST-2, GST-3, and TPST-2 79229.4 Assays for High-Throughput Screening of STs 79429.5 New Directions in Inhibitor Discovery 79629.6 Conclusions 79629.7 Acknowledgements 79629.8 References 79730 Carbohydrate-Based Treatment of Cancer Metastasis 803Reiji Kannagi30.1 Implication of Carbohydrate Determinants in Cancer Metastasis 80330.2 Tumor Angiogenesis and Cancer-Endothelial Interaction 80830.3 Use of Monoclonal Antibodies for Inhibition of Cancer Cell-Endothelial Interaction 80930.4 Inhibitors of Selectin-Mediated Cell Adhesion 81230.5 Regulation of Selectin Expression on Endothelial Cells 81430.6 Enhanced Expression of Sialyl Lex and Sialyl Lea in Malignant Cells and its Modulation 81630.7 References 82431 N-Acetylneuraminic Acid Derivatives and Mimetics as Anti-Influenza Agents 831Robin Thomson and Mark von Itzstein31.1 Introduction 83131.2 Structure-Based Design of Inhibitors of Influenza Virus Sialidase 83631.3 Structure/Activity Relationship Studies of N-Acetylneuraminic Acid-Based Influenza Virus Sialidase Inhibitors 84031.4 Concluding Remarks 85631.5 Acknowledgements 85631.6 References 85732 Modified and Modifying Sugars as a New Tool for the Development of Therapeutic Agents – The Biochemically Engineered N-Acyl Side Chain of Sialic Acid: Biological Implications and Possible Uses in Medicine 863Rüdiger Horstkorte, Oliver T. Keppler, and Werner Reutter32.1 Introduction 86332.2 N-Acyl Side Chain-Modified Precursors of Sialic Acid 86532.3 Outlook 87132.4 Acknowledgements 87232.5 Abbreviations 87232.6 References 87233 Modified and Modifying Sugars as a New Tool for the Development of Therapeutic Agents – Glycosidated Phospholipids as a New Type of Antiproliferative Agents 875Kerstin Danker, Annette Fischer, and Werner Reutter33.1 Introduction 87533.2 Structures of Synthetic Glycosidated Phospholipid Analogues 87633.3 Antiproliferative Effect and Cytotoxicity of Glycosidated Phospholipid Analogues in Cell Culture Systems 87633.4 Effect of Glycosidated Phospholipid Analogues on Cell Matrix Adhesion 87833.5 Mechanisms of Action 87933.6 Outlook and New Developments 88033.7 Acknowledgements 88133.8 References 88134 Glycoside Primers and Inhibitors of Glycosylation 883Jillian R. Brown, Mark M. Fuster, and Jeffrey D. Esko34.1 Introduction 88334.2 Glycoside-Based Substrates 88334.3 Glycoside Primers – Xylosides 88434.4 Other Types of Primers 88534.5 Glycosides as Metabolic Decoys 88834.6 Analogues 89034.7 References 89235 Carbohydrate-Based Drug Discovery in the Battle Against Bacterial Infections: New Opportunities Arising from Programmable One-Pot Oligosaccharide Synthesis 899Thomas K. Ritter and Chi-Huey Wong35.1 Introduction 89935.2 Cell-Surface Carbohydrates 90035.3 Peptidoglycan 90435.4 Macrolide Antibiotics 91335.5 Aminoglycosides 91735.6 Programmable One-Pot Oligosaccharide Synthesis 92235.7 Summary 92735.8 References 928Subject Index 933

"In summary, Carbohydrate-Based Drug Discovery Vols. 1 and 2 provide an appropriate and useful look at the current state of the art in this relevant and rapidly advancing field. I recommend the book to both experts and less expert readers." Francesco Nicotra, Universita di Milano-Bicocca (Italy)ChemBioChem 4/2004 "To summarize, the work provides a comprehensive and excellent survey of the present situation in carbohydrate research, in which many interesting details can be spotted. Because of the wide range of topics covered, the reader will refer to it again and again. It is likely to become a standard work on the subject, not exclusively for carbohydrate chemistry enthusiasts." Oliver Plettenburg, Ulrich StilzAngewandte Chemie + IE 2004-43/31