Note: Intro -- Title -- Copyright -- Preface -- Contents -- CHAPTER 1 Introduction: General Aspects of the Chemical Biology of Glycoproteins -- 1.1 Introduction -- 1.1.1 Complexity of Protein Glycosylation -- 1.1.2 Strategies and Methods to Study Protein Glycosylation -- 1.2 Chemical Biology of Glycoproteins -- 1.2.1 Types of Protein Glycosylation -- 1.2.2 Biosynthesis of Glycoproteins -- 1.2.3 Structural and Functional Consequences of Protein Glycosylation -- 1.2.4 Methods to Prepare Homogeneous Glycopeptides and Glycoproteins -- 1.2.5 Chemical Glycobiology and Applications -- 1.3 Conclusion -- References -- CHAPTER 2 Chemical Biology of Protein N-Glycosylation -- 2.1 Introduction -- 2.2 Biosynthesis and Intracellular Functions of N-Glycans of Glycoproteins -- 2.3 Inhibitors of Glycan-Processing Enzymes for Controlling Protein N-Glycosylation -- 2.4 Global Metabolic Enzyme Inhibitors for Perturbing Protein N-Glycosylation -- 2.5 Metabolic Glycoengineering of Cell-Surface Glycoproteins -- 2.6 Chemoenzymatic Synthesis and Glycosylation Remodeling Toward Homogeneous N-Glycoproteins -- 2.6.1 Generation of Novel ENGase-Based Glycosynthases for N-Glycosylation Remodeling and N-Glycoprotein Synthesis -- 2.6.2 Chemoenzymatic Fc Glycan Remodeling of Therapeutic Monoclonal Antibodies -- 2.6.3 Combined E. coli Expression and Chemoenzymatic Glycan Remodeling to Produce Humanized N-Glycoproteins -- 2.7 Conclusion -- Acknowledgements -- References -- CHAPTER 3 Chemical Biology of Protein O-Glycosylation -- 3.1 Introduction -- 3.2 Biosynthesis of O-Glycoproteins -- 3.2.1 α-O-GalNAc -- 3.2.2 α-O-Man -- 3.2.3 α-O-Fuc -- 3.2.4 β-O-Glc -- 3.2.5 β-O-GlcNAc -- 3.3 Chemical Biology in Studying the Structural and Functional Consequences of Protein O-Glycosylation -- 3.3.1 α-O-GalNAc -- 3.3.1.1 Substrate Preferences of ppGalNAcTs. , 3.3.1.2 Structural Effects of O-GalNAc Glycosylation -- 3.3.1.3 Functional Effects of O-GalNAc Glycosylation -- 3.3.2 α-O-Man -- 3.3.2.1 Biosynthetic Pathway of O-Man Glycans -- 3.3.2.2 Biophysical and Biological Effects of O-Mannosylation -- 3.3.3 α-O-Fuc -- 3.3.4 β-O-Glc -- 3.3.5 β-O-GlcNAc -- 3.4 Chemical Biology in Studying the Composition of Mixtures of O-Glycoproteins -- 3.4.1 Glycoprotein Purification and Enrichment -- 3.4.2 Glycoprotein Digestion and Glycopeptide Separation -- 3.4.3 Glycopeptide Analysis -- 3.4.4 Importance of Synthetic Glycopeptides in Protein Glycosylation Analysis -- 3.5 Conclusion -- References -- CHAPTER 4 Chemical Biology of O-GlcNAc Glycosylation -- 4.1 Introduction -- 4.2 Chemical Blockade of O-GlcNAc Addition -- 4.2.1 Inhibitors of UDP-GlcNAc Biosynthesis -- 4.2.2 Product Inhibition of OGT: UDP -- 4.2.3 Alloxan -- 4.2.4 Screening Approaches to Discover OGT Inhibitors -- 4.2.5 Substrate Mimicry Approach to Discover OGT Inhibitors -- 4.2.6 New Directions in OGT Inhibitor Development -- 4.3 Chemical Blockade of O-GlcNAc Removal: OGA Inhibitors -- 4.3.1 Streptozotocin -- 4.3.2 PUGNAc -- 4.3.3 NAG-Thiazoline -- 4.3.4 GlcNAcstatins -- 4.3.5 Thiamet-G -- 4.3.6 Other Approaches to OGA Inhibition -- 4.4 Detection of O-GlcNAcylated Substrates: Lectins and Antibodies -- 4.5 Detection of O-GlcNAcylated Substrates: Mass Spectrometry-Based Methods -- 4.5.1 Electron Transfer Dissociation MS -- 4.5.2 MS Approaches to Complement ETD -- 4.5.3 Chemical Derivatization of MS Samples for O-GlcNAc Enrichment and Detection -- 4.6 Detection of O-GlcNAcylated Substrates: A Chemoenzymatic Approach -- 4.7 Detection of O-GlcNAcylated Substrates: Metabolic Labeling Approaches -- 4.7.1 N-Azidoacetylglucosamine (GlcNAz) -- 4.7.2 N-Azidoacetylgalactosamine (GalNAz) -- 4.7.3 N-Butynyl-Glucosamine (GlcNAlk) and Other Alkynylsugars. , 4.7.4 Other Metabolic Labeling Reagents -- 4.8 Methods to Deduce the Biochemical and Cellular Functions of O-GlcNAc -- 4.8.1 Live-Cell Assays of OGT or OGA Activity -- 4.8.2 Chemical Modification and Semi-Synthesis of Model Glycoproteins and Glycopeptides -- 4.8.3 Photocrosslinking Tools to Capture O-GlcNAc-Mediated Protein-Protein Interactions -- 4.9 Conclusions and Outlook -- References -- CHAPTER 5 Chemical Synthesis and Engineering of N-Linked Glycoproteins -- 5.1 Introduction -- 5.2 Semisynthesis of N-Glycosylated Proteins -- 5.2.1 Semisynthesis of N-Glycoprotein Mimics with Unnatural Glycosyl Linkages at Cysteines -- 5.2.2 Semisynthesis of Glycoproteins with Natural N-Linkages on Asparagines -- 5.3 Total Chemical Synthesis of N-Linked Glycoproteins -- 5.3.1 Total Synthesis of N-Linked Glycoproteins Bearing N-Chitobioses -- 5.3.2 Total Synthesis of N-Linked Glycoproteins Bearing "Wild-Type" N-Glycans -- 5.3.3 Representative Synthetic Attempts Towards Producing N-Linked Glycoproteins with Multiple Disulfide Linkages -- 5.4 Application of Chemically Synthesized N-Linked Glycoproteins to Biological Processes -- 5.5 Conclusion -- References -- CHAPTER 6 Chemoenzymatic Synthesis of N-Glycans -- 6.1 Introduction -- 6.2 Chemical Synthesis of Complex N-Glycans -- 6.2.1 Assembly Strategy and Method of Glycosylation in Chemical Synthesis of N-Glycans -- 6.2.2 Total Synthesis of Complex N-Glycans by Global Glycosylation of a Core Pentasaccharide -- 6.2.3 Convergent Synthesis of Complex N-Glycans by Glycosylation of Core Trisaccharide -- 6.3 Chemoenzymatic Synthesis of Complex N-Glycans -- 6.3.1 A General Strategy for the Chemoenzymatic Synthesis of Asymmetrically Branched N-Glycans -- 6.3.1.1 Chemical Synthesis of Asymmetric N-Glycans by Orthogonal Protection Strategy -- 6.3.1.2 Enzymatic Extension to Synthesize Asymmetrically Branched N-Glycans. , 6.3.2 Core Synthesis/Enzymatic Extension (CSEE) Strategy for Efficient Synthesis of N-Glycan Libraries -- 6.3.2.1 Chemical Synthesis of N-Glycan Core Structures Through Convergent Block Coupling -- 6.3.2.2 Enzymatic Extension to Obtain a N-Glycan Library -- 6.4 Conclusion -- References -- CHAPTER 7 Towards Synthesis of Heparan Sulfate Glycopeptides and Proteoglycans -- 7.1 Structures, Biological Functions and Biosynthesis of Proteoglycans -- 7.2 Chemical Synthesis of the PG Linker-Peptide Conjugates -- 7.3 Synthesis of HS Glycopeptides -- 7.4 Conclusion and Future Outlook -- Acknowledgements -- References -- CHAPTER 8 Chemoenzymatic Synthesis of Low-Molecular-Weight Heparin and Heparan Sulfate -- 8.1 Introduction -- 8.1.1 What are Heparan Sulfate, Heparin and Heparin-Derivatives? -- 8.1.2 Why are Synthetic Heparins and Heparan Sulfates Needed? -- 8.1.3 Types of Chemoenzymatic Synthesis -- 8.2 Enzymes Required for Chemoenzymatic Synthesis -- 8.2.1 Glycosyltransferases -- 8.2.2 Sulfotransferases and C5-Epimerase -- 8.3 Building Blocks Prepared for Chemoenzymatic Synthesis -- 8.3.1 Acceptors -- 8.3.2 Donors -- 8.3.2.1 Natural UDP-Sugars -- 8.3.2.2 Unnatural UDP-Sugars -- 8.3.3 Polysaccharide and Oligosaccharide Backbone -- 8.4 Control of Product Through Sequential Enzymatic Modification -- 8.5 Novel Chemoenzymatic Synthesis -- 8.5.1 One-Pot Multienzyme System -- 8.5.2 Fluorous-Tagging Techniques -- 8.5.3 Solid-Phase Synthesis -- 8.5.4 Immobilized Enzymes -- 8.5.5 Immobilized Enzyme Cofactors -- 8.6 Conclusion and Future Perspectives -- References -- CHAPTER 9 Synthetic Studies of GPI-Anchored Peptides, Glycopeptides, and Proteins -- 9.1 Introduction -- 9.2 Biosynthesis of GPIs and GPI-Anchored Proteins -- 9.2.1 Biosynthesis of GPI Anchors -- 9.2.2 Posttranslational Attachment of GPIs to Proteins. , 9.3 Synthesis of GPI-Anchored Proteins and Glycoproteins -- 9.3.1 Chemical Total Synthesis of GPI-Anchored Peptides and Glycopeptides -- 9.3.2 Synthesis of GPI-Anchored Peptides and Proteins via NCL -- 9.3.3 Synthesis of GPI-Anchored Peptides, Glycopeptides, and Proteins via Enzymatic Ligation -- 9.4 GPI-Anchored Proteomics Studies -- 9.5 Concluding Remarks -- Acknowledgements -- References -- CHAPTER 10 Chemical Approaches to Image Protein Glycosylation -- 10.1 Background -- 10.2 Structure, Biosynthesis, and Function of Protein Glycans -- 10.2.1 N-Linked Glycans -- 10.2.2 Mucin-Type O-Linked Glycans -- 10.2.3 Sialic Acids -- 10.2.4 O-GlcNAc -- 10.3 Methods for Glycan Labeling and Imaging -- 10.3.1 Lectins and Antibodies -- 10.3.2 Metabolic Glycan Labeling -- 10.3.3 Chemoenzymatic Labeling -- 10.4 Imaging Protein Glycosylation -- 10.4.1 General Principles of the Dual-Labeling-Based Methods -- 10.4.2 FRET-Based Protein-Specific Imaging of Glycosylation -- 10.4.3 PLA-Based Protein-Specific Imaging of Glycosylation -- 10.4.4 Protein-Specific Imaging of Glycosylation Based on PEBL -- 10.4.5 Protein-Specific Imaging of Glycosylation Based on SERS -- 10.5 Conclusion and Perspective -- References -- CHAPTER 11 Targeting Glycans of HIV Envelope Glycoproteins for Vaccine Design -- 11.1 The Human Immunodeficiency Virus -- 11.1.1 Structure, Genome and Viral Lifecycle -- 11.1.2 Transmission and Pathogenesis -- 11.1.3 The Viral Envelope is the Main Target for the Immune System -- 11.1.4 Immune Response -- 11.1.5 Current Therapies and Steps towards a Vaccine -- 11.2 The Viral Envelope Spike -- 11.2.1 Biosynthesis -- 11.2.2 Structure and Function of Env -- 11.2.3 The Glycan Shield -- 11.2.4 Site-specific N-Linked Glycan Analysis -- 11.2.5 Glycans in Immune Escape -- 11.3 A Target for Broadly Neutralizing Antibodies -- 11.3.1 Sites of Vulnerability. , 11.3.2 Unusual Features of Broadly Neutralizing Antibodies.

Note: Front Cover -- Chemistry and Biology of Heparin and Heparan Sulfate -- Copyright Page -- Contents -- Preface -- Contributors -- Chapter 1. Structure and Active Domains of Heparin -- I .Introduction -- II. Heparin Components -- III. Molecular Conformation of Heparin Residues and Sequences -- IV. Heparin Domains Involved in Biological Interactions -- V. Molecular Conformation of Active Domains -- VI. Conclusions -- Chapter 2. Structure and Function of Cell Associated and Pericellular Heparan Sulfate Proteoglycans -- I. Introduction -- II. Heparan Sulfate Synthesis -- III. Molecular Structure of Heparan Sulfate and Binding Ligands -- IV. Types of Heparan Sulfate Proteoglycans -- V. Syndecans -- VI. Role of Syndecan in Development -- VII. Glypicans -- VIII. Roles of Glypican in Tissue Development -- IX. Betaglycan and CD44 -- X. Pericellular Heparan Sulfate Proteoglycans -- XI. Role in Disease Pathogenesis -- XII. Summary -- Chapter 3. Methods for Structural Analysis of Heparin and Heparan Sulfate -- I. Introduction -- II. Structure of Heparin and Heparan Sulfate -- III. Separation-Based Analysis of Heparin and Heparan Sulfate -- IV. Mass Spectrometric Analysis of Heparin and Heparan Sulfate -- V. Nuclear Magnetic Resonance Analysis of Heparin and Heparan Sulfate -- VI. New Methodologies for Structural Analysis of Heparin and Heparan Sulfate -- VII. Summary and Conclusions -- Chapter 4. Synthetic Approach to Define Structure-Activity Relationship of Heparin and Heparan Sulfate -- I. Introduction -- II. Biosynthesis -- III. Structure of Heparin/Heparan Sulfate -- IV. Chemical Synthesis of Defined Heparin Oligosaccharides -- V. Summary and Outlook -- Chapter 5. Biochemical and Pharmacological Rationale for Synthetic Heparin Polysaccharides -- I. Introduction -- II. Biological Activities and Mechanisms of Action of Heparin. , III. Fractionation and Fragmentation of Heparin -- IV. Elucidation of the Minimum Heparin Sequence for Binding to AT -- V. Synthesis of the Pentasaccharide Representing the Critical Binding Site of Heparin to AT -- VI. Pre-Clinical Pharmacology of Fondaparinux -- VII. Clinical Trials of Fondaparinux -- VIII. Derivatives of Pentasaccharide -- IX. Summary -- Chapter 6.Seperation and Sequencing of Heparin and Heparan Sulphate Saccharides -- I. Introduction -- II. Seperation of Heparin and Heparan Sulphate Oligosaccharides -- III. Heparin and Heparan Sulphate Sequencing -- IV. Discussion -- Chapter 7. Biosynthesis of Heparin and Heparan Sulfate -- I. Introduction -- II. Biosynthetic Enzymes and Transporters of Uridine Diphosphate- Sugars and 3'-Phosphoadenosine 5'-Phosphosulfate -- III. Biosynthesis of Heparin and Heparan Sulfate Backbones -- IV. Modification of the Sugar Backbones of Heparin and Heparan Sulfate -- V. Conclusions -- Chapter 8. Remodeling of Heparan Sulfation by Extracellular Endosulfatases -- I. Introduction -- II. Identification of Sulf Enzymes -- III. Expression and Enzymatic Activity of Sulf Enzymes -- IV. Signaling Regulatory Functions of Extracellular Sulfatases -- V. Sulf Function in Tumor and Angiogenesis -- VI. Conclusions -- Chapter 9. Heparan Sulfate Degradation by Heparanases -- I. Heparanase Proteins -- II. Synthesis of Heparanase 1 -- III. Heparanase 1 Catalytic Activity -- IV. Biological Functions of Heparanase 1 -- Chapter 10. Lysosomal Degradation of Heparin and Heparan Sulfate -- I. Introduction -- II. Transport of Heparin and Heparan Sulfate to the Lysosome -- III. endo-Degradation of Heparin and Heparan Sulfate -- IV. exo-Degradation of Heparin and Heparan Sulfate -- V. Transport of Degradation Products out of the Lysosome -- VI. Diagnostic and Clinical Aspects of the Mucopolysaccharides. , VII. Summary and Future Challenges in the Field -- Chapter 11. Heparin Regulation of the Complement System -- I . Introduction -- II. Background and History -- III. Heparin Regulation of the Complement System -- IV.The Effects of Heparin on the Alternative Pathway -- V . Conclusions -- Chapter 12 . Surface-Based Studies of Heparin/Heparan Sulfate-Protein Interactions: Considerations for Surface Immobilisation of HS/Heparin Saccharides and Monitoring Their Interactions with Binding Proteins -- I . Introduction -- II . Attachment -- III . Methods of Attachment to Surfaces -- IV . Detection of Binding Partners -- Chapter 13 . Heparin Activation of Serpins -- I . Introduction -- II . General Features of Heparin Binding Serpins -- III . Antithrombin -- IV . Heparin Cofactor II -- V . The Others -- VI . Conclusions -- Chapter 14. Role of Heparan Sulfate in Fibroblast Growth Factor Signaling -- I . Introduction and Perspective -- II . Fibroblast Growth Factors -- III . FGF receptors -- IV.Interactions of the FGFs and FGFRs with Heparin -- V. Structural Studies of FGF, FGFR and Heparin Complexes -- VI. Conclusions and Future Perspectives -- Chapter 15. Role of Anticoagulant Heparan Sulfate in Mammalian Reproduction -- I. Introduction. -- II. Anticoagulant Heparan Sulfate Proteogly -- III. Anticoagulant Heparan Sulfate Proteoglycans in the Reproductive Tract -- IV. Reproduction in Mice Deficient in Anticoagulant Heparan Sulfate Proteoglycans -- V. Perspectives. -- Chapter 16. Glycol-Splitting as a Device for Modulating Inhibition of Growth Factors and Heparanase by Heparin and Heparin Derivatives -- I. Introduction. -- II. Glycol-Split Heparins -- III. Protein-Binding and Associated Biological Properties of Glycol-Split Heparins -- IV. Conformational Implications of Glycol- Splitting -- V. Conclusions. , Chapter 17. Antithrombin Activation and Designing Novel Heparin Mimics -- I. Introduction -- II. Antithrombin Inhibition of Procoagulant Proteinases -- III. Structure of Heparin and Heparin Pentasaccharide -- IV. Mechanism of Heparin Activation of Antithrombin -- V. The Heparin Binding Site in Antithrombin -- VI. The Heparin Binding Site in Factor xa and Thrombin -- VII. Thermodynamics and kinetics of Heparin Binding to Antithrombin -- VIII. Rationale for Designing Functrional Mimics of Heparin -- IX. Heparin Mimics -- X. Conclusions -- Chapter 18. Influence of Heparin Chemical Modifications on Its Antiproliferative Properties. -- I. Introduction -- II. Background and Significance of Chemical Modification of Heparin -- III. Mechanisms Contributing to Heparin Inhibition of Smooth Muscle Cell Growth -- IV. Importance of 3-0-Sulfo Group on the Internal Glucosamine Residue of Pentasaccharide for Antiproliferative Activity -- V. Minimal Heparin Oligosaccharide Size Necessary for Antiproliferative Activity -- VI. Effect of Chemical Modification of Heparin on Its Antiproliferative Activity -- VII. Effect of the Type of Serum on Antiproliferative Activity -- VIII. Conclusions -- Chapter 19. Mechanisms of Cell Growth Regulation by Heparin and Heparan Sulfate -- I. Introduction. -- II. Modulation of Growth Factor Action -- III. Direct Regulation of Cell Growth -- IV. Growth Control in Disease -- V. Conclusions -- Chapter 20. Heparin and Low Molecular Weight Heparin in Thrombosis and Inflammation: Emerging Link -- I. Introduction -- II. Emerging Links Between Thrombosis and Inflammation: Potential Role of Heparin -- III. Heparin versus Low Molecular Weight Heparin -- IV. Heparin as an Anti-Inflammatory Molecule: Potential Mechanisms -- V. Conclusions -- Chapter 21. Basic and Clinical Differences of Heparin and Low Molecular Weight Heparin Treatment. , I. Introduction. -- II. Unfractionated Heparin and Newer Anticoagulant and Antithrombotic Drugs -- III. Low Molecular Weight Heparins and Their Impact on the Management of Thromnbotic and Vascular Disorders -- IV. Monitoring of Heparin and Low Molecular Weight Heparins. -- V. Clinical Trials with Low Molecular Weight Heparins -- VI. Generic Low Molecular Weight Heparins.. -- VII. American College of Chest Physicians Consensus Recommendations -- VIII. Summary -- Chapter 22. Perlecan: An Extracellular Matrix Heparan Sulfate Proteoglycan that Regulates Key Events in Vascular Development and Disease -- I. Introduction. -- II. Perlecan-The Gene, the Protein Core, and the Glycosaminoglycans -- III. Perlecan is a Key Extracellular Matrix Component in Basement Membranes and in the Development of the Vascular System -- IV. Phenotypic Regulation of Vascular Cells by Perlecan -- V.Perlecan in Intimal Hyperplasia -- VI. Perlecan in Atherosclerosis -- VII. Perlecan and Angiogenesis -- VIII. Conclusions -- Chapter 23. Heparin and Low Molecular Weight Heparins in Clinical Cardiology -- I. Introduction -- II.Overview of Pharmacology -- III. Clinical Experience -- IV. Conclusions -- Chapter 24. Heparin-Induced Thrombocytopenia -- I. Introduction -- II. Pathogenesis -- III. Clinical Picture -- IV. Laboratory Testing for Heparin-Induced Thrombocytopenia Antibodies -- V. Treatment -- Chapter 25. Role of Heparan Sulfate in Cancer.. -- I. Introduction. -- II. Structure Features of Glycosaminoglycans -- III. Biosynthesis and Degradation of Heparan Sulfate Glycosaminoglycans -- IV. Biological Functions of Heparan Sulfate Glycosaminoglycans -- V. Heparan Sulfate Glycosaminoglycans in Cancer -- Chapter 26. Use of Heparin Preparations in Older Patients -- I. Introduction.. -- II. Aging and the Haemostatic System. , III. Unfractionated Heparin, Low Molecular Weight Heparins, and Fondaparinux: Pharmacological Properties.