Elsevier S & T

Chemistry and Biology of Heparin and Heparan Sulfate

Garg, Hari G.; Linhardt, Robert J.; Hales, Charles A.

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Table of contents

Contentsxiii
Prefacevii
Contributorsix
Chapter 1. Structure and Active Domains of Heparin1
I .Introduction1
II. Heparin Components2
III. Molecular Conformation of Heparin Residues and Sequences9
IV. Heparin Domains Involved in Biological Interactions11
V. Molecular Conformation of Active Domains17
VI. Conclusions19
Chapter 2. Structure and Function of Cell Associated and Pericellular Heparan Sulfate Proteoglycans29
I. Introduction29
II. Heparan Sulfate Synthesis30
III. Molecular Structure of Heparan Sulfate and Binding Ligands30
IV. Types of Heparan Sulfate Proteoglycans33
V. Syndecans33
VI. Role of Syndecan in Development35
VII. Glypicans37
VIII. Roles of Glypican in Tissue Development39
IX. Betaglycan and CD4440
X. Pericellular Heparan Sulfate Proteoglycans41
XI. Role in Disease Pathogenesis43
XII. Summary45
Chapter 3. Methods for Structural Analysis of Heparin and Heparan Sulfate55
I. Introduction55
II. Structure of Heparin and Heparan Sulfate56
III. Separation-Based Analysis of Heparin and Heparan Sulfate57
IV. Mass Spectrometric Analysis of Heparin and Heparan Sulfate62
V. Nuclear Magnetic Resonance Analysis of Heparin and Heparan Sulfate67
VI. New Methodologies for Structural Analysis of Heparin and Heparan Sulfate70
VII. Summary and Conclusions71
Chapter 4. Synthetic Approach to Define Structure-Activity Relationship of Heparin and Heparan Sulfa79
I. Introduction79
II. Biosynthesis80
III. Structure of Heparin/Heparan Sulfate82
IV. Chemical Synthesis of Defined Heparin Oligosaccharides84
V. Summary and Outlook129
Chapter 5. Biochemical and Pharmacological Rationale for Synthetic Heparin Polysaccharides143
I. Introduction143
II. Biological Activities and Mechanisms of Action of Heparin144
III. Fractionation and Fragmentation of Heparin147
IV. Elucidation of the Minimum Heparin Sequence for Binding to AT152
V. Synthesis of the Pentasaccharide Representing the Critical Binding Site of Heparin to AT154
VI. Pre-Clinical Pharmacology of Fondaparinux155
VII. Clinical Trials of Fondaparinux159
VIII. Derivatives of Pentasaccharide160
IX. Summary163
Chapter 6.Seperation and Sequencing of Heparin and Heparan Sulphate Saccharides179
I. Introduction179
II. Seperation of Heparin and Heparan Sulphate Oligosaccharides181
III. Heparin and Heparan Sulphate Sequencing192
IV. Discussion198
Chapter 7. Biosynthesis of Heparin and Heparan Sulfate203
I. Introduction203
II. Biosynthetic Enzymes and Transporters of Uridine Diphosphate- Sugars and 3'-Phosphoadenosine 5'-205
III. Biosynthesis of Heparin and Heparan Sulfate Backbones208
IV. Modification of the Sugar Backbones of Heparin and Heparan Sulfate220
V. Conclusions226
Chapter 8. Remodeling of Heparan Sulfation by Extracellular Endosulfatases245
I. Introduction245
II. Identification of Sulf Enzymes246
III. Expression and Enzymatic Activity of Sulf Enzymes248
IV. Signaling Regulatory Functions of Extracellular Sulfatases249
V. Sulf Function in Tumor and Angiogenesis253
VI. Conclusions255
Chapter 9. Heparan Sulfate Degradation by Heparanases259
I. Heparanase Proteins259
II. Synthesis of Heparanase 1261
III. Heparanase 1 Catalytic Activity269
IV. Biological Functions of Heparanase 1275
Chapter 10. Lysosomal Degradation of Heparin and Heparan Sulfate285
I. Introduction285
II. Transport of Heparin and Heparan Sulfate to the Lysosome286
III. endo-Degradation of Heparin and Heparan Sulfate286
IV. exo-Degradation of Heparin and Heparan Sulfate291
V. Transport of Degradation Products out of the Lysosome298
VI. Diagnostic and Clinical Aspects of the Mucopolysaccharides299
VII. Summary and Future Challenges in the Field303
Chapter 11. Heparin Regulation of the Complement System313
I . Introduction313
II. Background and History314
III. Heparin Regulation of the Complement System318
IV.The Effects of Heparin on the Alternative Pathway330
V . Conclusions337
Chapter 12 . Surface-Based Studies of Heparin/Heparan Sulfate-Protein Interactions: Considerations f345
I . Introduction345
II . Attachment347
III . Methods of Attachment to Surfaces354
IV . Detection of Binding Partners356
Chapter 13. Heparin Activation of Serpins367
I . Introduction367
II . General Features of Heparin Binding Serpins368
III . Antithrombin373
IV . Heparin Cofactor II379
V . The Others382
VI . Conclusions388
Chapter 14. Role of Heparan Sulfate in Fibroblast Growth Factor Signaling399
I . Introduction and Perspective399
II . Fibroblast Growth Factors400
III . FGF receptors402
IV.Interactions of the FGFs and FGFRs with Heparin405
V. Structural Studies of FGF, FGFR and Heparin Complexes414
VI. Conclusions and Future Perspectives426
Chapter 15. Role of Anticoagulant Heparan Sulfate in Mammalian Reproduction435
I. Introduction.435
II. Anticoagulant Heparan Sulfate Proteogly435
III. Anticoagulant Heparan Sulfate Proteoglycans in the Reproductive Tract437
IV. Reproduction in Mice Deficient in Anticoagulant Heparan Sulfate Proteoglycans451
V. Perspectives.453
Chapter 16. Glycol-Splitting as a Device for Modulating Inhibition of Growth Factors and Heparanase461
I. Introduction.461
II. Glycol-Split Heparins462
III. Protein-Binding and Associated Biological Properties of Glycol-Split Heparins467
IV. Conformational Implications of Glycol- Splitting474
V. Conclusions476
Chapter 17. Antithrombin Activation and Designing Novel Heparin Mimics483
I. Introduction483
II. Antithrombin Inhibition of Procoagulant Proteinases486
III. Structure of Heparin and Heparin Pentasaccharide487
IV. Mechanism of Heparin Activation of Antithrombin488
V. The Heparin Binding Site in Antithrombin491
VI. The Heparin Binding Site in Factor xa and Thrombin493
VII. Thermodynamics and kinetics of Heparin Binding to Antithrombin494
VIII. Rationale for Designing Functrional Mimics of Heparin496
IX. Heparin Mimics497
X. Conclusions504
Chapter 18. Influence of Heparin Chemical Modifications on Its Antiproliferative Properties.513
I. Introduction513
II. Background and Significance of Chemical Modification of Heparin514
III. Mechanisms Contributing to Heparin Inhibition of Smooth Muscle Cell Growth515
IV. Importance of 3-0-Sulfo Group on the Internal Glucosamine Residue of Pentasaccharide for Antipro516
V. Minimal Heparin Oligosaccharide Size Necessary for Antiproliferative Activity517
VI. Effect of Chemical Modification of Heparin on Its Antiproliferative Activity519
VII. Effect of the Type of Serum on Antiproliferative Activity524
VIII. Conclusions528
Chapter 19. Mechanisms of Cell Growth Regulation by Heparin and Heparan Sulfate533
I. Introduction.533
II. Modulation of Growth Factor Action534
III. Direct Regulation of Cell Growth544
IV. Growth Control in Disease546
V. Conclusions553
Chapter 20. Heparin and Low Molecular Weight Heparin in Thrombosis and Inflammation: Emerging Link571
I. Introduction571
II. Emerging Links Between Thrombosis and Inflammation: Potential Role of Heparin572
III. Heparin versus Low Molecular Weight Heparin575
IV. Heparin as an Anti-Inflammatory Molecule: Potential Mechanisms577
V. Conclusions578
Chapter 21. Basic and Clinical Differences of Heparin and Low Molecular Weight Heparin Treatment583
I. Introduction.583
II. Unfractionated Heparin and Newer Anticoagulant and Antithrombotic Drugs584
III. Low Molecular Weight Heparins and Their Impact on the Management of Thromnbotic and Vascular Di589
IV. Monitoring of Heparin and Low Molecular Weight Heparins.594
V. Clinical Trials with Low Molecular Weight Heparins597
VI. Generic Low Molecular Weight Heparins..598
VII. American College of Chest Physicians Consensus Recommendations600
VIII. Summary603
Chapter 22. Perlecan: An Extracellular Matrix Heparan Sulfate Proteoglycan that Regulates Key Events607
I. Introduction.607
II. Perlecan-The Gene, the Protein Core, and the Glycosaminoglycans607
III. Perlecan is a Key Extracellular Matrix Component in Basement Membranes and in the Development610
IV. Phenotypic Regulation of Vascular Cells by Perlecan611
V.Perlecan in Intimal Hyperplasia615
VI. Perlecan in Atherosclerosis618
VII. Perlecan and Angiogenesis621
VIII. Conclusions623
Chapter 23. Heparin and Low Molecular Weight Heparins in Clinical Cardiology637
I. Introduction637
II.Overview of Pharmacology637
III. Clinical Experience641
IV. Conclusions662
Chapter 24. Heparin-Induced Thrombocytopenia673
I. Introduction673
II. Pathogenesis673
III. Clinical Picture677
IV. Laboratory Testing for Heparin-Induced Thrombocytopenia Antibodies679
V. Treatment680
Chapter 25. Role of Heparan Sulfate in Cancer..699
I. Introduction.699
II. Structure Features of Glycosaminoglycans699
III. Biosynthesis and Degradation of Heparan Sulfate Glycosaminoglycans702
IV. Biological Functions of Heparan Sulfate Glycosaminoglycans703
V. Heparan Sulfate Glycosaminoglycans in Cancer706
Chapter 26. Use of Heparin Preparations in Older Patients727
I. Introduction..727
II. Aging and the Haemostatic System728
III. Unfractionated Heparin, Low Molecular Weight Heparins, and Fondaparinux: Pharmacological Proper729
IV. Unfractionated Heparin, Low Molecular Weight Heparins, and Fondaparinux: Clinical Use in Elderly731
V. Heparin and Low Molecular Weight Heparins: Risk of Bleeding in the Elderly734
VI. Conclusions and Perspectives737
Chapter 27. Advances in Low Molecular Weight Heparin Use in Pregnancy745
I. Introduction745
II. Pharmacology a Pharmacokinetics of Low Molecular Weight Heparin in Preganancy745
III. Indications for the Use of Low Molecular Weight Heparin in Pregnancy748
IV. Safety of Low Molecular Weight Heparin in Pregnancy759
V. Conclusions761
Subject Index769

Book details

Vendor Elsevier S & T
SKU 9780080448596
ISBN-13 9780080529059
Author Garg, Hari G.; Linhardt, Robert J.; Hales, Charles A.
Category Science
Subject Organic

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The chemistry, biochemistry and pharmacology of heparin and heparan sulfate have been and continue to be a major scientific undertaking - heparin and its derivative remain important drugs in clinical practice. Chemistry and Biology of Heparin and Heparan Sulfate provides readers with an insight into the chemistry, biology and clinical applications of heparin and heparan sulfate and examines their function in various physiological and pathological conditions. Providing a wealth of useful information, no other tome covers the diversity of topics in the field. Students, doctors, chemists, biochemists, and research scientists will find this book an invaluable source for updating their current knowledge of developments in this area.

* Comprehensively reviews all aspects of heparin and heparan sulfate research
* Uniquely describes the chemistry, biology and clinical application of heparins and heparan sulfates in one work
* Provides an invaluable source of knowledge of current developments for chemists, biochemists, medical doctors, researchers, students and practitioners

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