Garg / Linhardt / Hales Chemistry and Biology of Heparin and Heparan Sulfate

1. Auflage 2011
ISBN: 978-0-08-052905-9
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 792 Seiten

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

Autoren/Hrsg.

Garg, Hari G.

Linhardt, Robert J.

Hales, Charles A.

Inhaltsverzeichnis

1;Cover
;1
2;Contents;14
3;Preface;8
4;Contributors;10
5;Chapter 1. Structure and Active Domains of Heparin;20
5.1;I .Introduction;20
5.2;II. Heparin Components;21
5.3;III. Molecular Conformation of Heparin Residues and Sequences;28
5.4;IV. Heparin Domains Involved in Biological Interactions;30
5.5;V. Molecular Conformation of Active Domains;36
5.6;VI. Conclusions;38
6;Chapter 2. Structure and Function of Cell Associated and Pericellular Heparan Sulfate Proteoglycans;48
6.1;I. Introduction;48
6.2;II. Heparan Sulfate Synthesis;49
6.3;III. Molecular Structure of Heparan Sulfate and Binding Ligands;49
6.4;IV. Types of Heparan Sulfate Proteoglycans;52
6.5;V. Syndecans;52
6.6;VI. Role of Syndecan in Development;54
6.7;VII. Glypicans;56
6.8;VIII. Roles of Glypican in Tissue Development;58
6.9;IX. Betaglycan and CD44;59
6.10;X. Pericellular Heparan Sulfate Proteoglycans;60
6.11;XI. Role in Disease Pathogenesis;62
6.12;XII. Summary;64
7;Chapter 3. Methods for Structural Analysis of Heparin and Heparan Sulfate;74
7.1;I. Introduction;74
7.2;II. Structure of Heparin and Heparan Sulfate;75
7.3;III. Separation-Based Analysis of Heparin and Heparan Sulfate;76
7.4;IV. Mass Spectrometric Analysis of Heparin and Heparan Sulfate;81
7.5;V. Nuclear Magnetic Resonance Analysis of Heparin and Heparan Sulfate;86
7.6;VI. New Methodologies for Structural Analysis of Heparin and Heparan Sulfate;89
7.7;VII. Summary and Conclusions;90
8;Chapter 4. Synthetic Approach to Define Structure-Activity Relationship of Heparin and Heparan Sulfate;98
8.1;I. Introduction;98
8.2;II. Biosynthesis;99
8.3;III. Structure of Heparin/Heparan Sulfate;101
8.4;IV. Chemical Synthesis of Defined Heparin Oligosaccharides;103
8.5;V. Summary and Outlook;148
9;Chapter 5. Biochemical and Pharmacological Rationale for Synthetic Heparin Polysaccharides;162
9.1;I. Introduction;162
9.2;II. Biological Activities and Mechanisms of Action of Heparin;163
9.3;III. Fractionation and Fragmentation of Heparin;166
9.4;IV. Elucidation of the Minimum Heparin Sequence for Binding to AT;171
9.5;V. Synthesis of the Pentasaccharide Representing the Critical Binding Site of Heparin to AT;173
9.6;VI. Pre-Clinical Pharmacology of Fondaparinux;174
9.7;VII. Clinical Trials of Fondaparinux;178
9.8;VIII. Derivatives of Pentasaccharide;179
9.9;IX. Summary;182
10;Chapter 6.Seperation and Sequencing of Heparin and Heparan Sulphate Saccharides;198
10.1;I. Introduction;198
10.2;II. Seperation of Heparin and Heparan Sulphate Oligosaccharides;200
10.3;III. Heparin and Heparan Sulphate Sequencing;211
10.4;IV. Discussion;217
11;Chapter 7. Biosynthesis of Heparin and Heparan Sulfate;222
11.1;I. Introduction;222
11.2;II. Biosynthetic Enzymes and Transporters of Uridine Diphosphate- Sugars and 3'-Phosphoadenosine 5'-Phosphosulfate;224
11.3;III. Biosynthesis of Heparin and Heparan Sulfate Backbones;227
11.4;IV. Modification of the Sugar Backbones of Heparin and Heparan Sulfate;239
11.5;V. Conclusions;245
12;Chapter 8. Remodeling of Heparan Sulfation by Extracellular Endosulfatases;264
12.1;I. Introduction;264
12.2;II. Identification of Sulf Enzymes;265
12.3;III. Expression and Enzymatic Activity of Sulf Enzymes;267
12.4;IV. Signaling Regulatory Functions of Extracellular Sulfatases;268
12.5;V. Sulf Function in Tumor and Angiogenesis;272
12.6;VI. Conclusions;274
13;Chapter 9. Heparan Sulfate Degradation by Heparanases;278
13.1;I. Heparanase Proteins;278
13.2;II. Synthesis of Heparanase 1;280
13.3;III. Heparanase 1 Catalytic Activity ;288
13.4;IV. Biological Functions of Heparanase 1;294
14;Chapter 10. Lysosomal Degradation of Heparin and Heparan Sulfate ;304
14.1;I. Introduction;304
14.2;II. Transport of Heparin and Heparan Sulfate to the Lysosome ;305
14.3;III. endo-Degradation of Heparin and Heparan Sulfate;305
14.4;IV. exo-Degradation of Heparin and Heparan Sulfate;310
14.5;V. Transport of Degradation Products out of the Lysosome;317
14.6;VI. Diagnostic and Clinical Aspects of the Mucopolysaccharides;318
14.7;VII. Summary and Future Challenges in the Field;322
15;Chapter 11. Heparin Regulation of the Complement System;332
15.1;I . Introduction;332
15.2;II. Background and History;333
15.3;III. Heparin Regulation of the Complement System ;337
15.4;IV.The Effects of Heparin on the Alternative Pathway ;349
15.5;V . Conclusions;356
16;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;364
16.1;I . Introduction;364
16.2;II . Attachment;366
16.3;III . Methods of Attachment to Surfaces;373
16.4;IV . Detection of Binding Partners;375
17;Chapter 13. Heparin Activation of Serpins;386
17.1;I . Introduction;386
17.2;II . General Features of Heparin Binding Serpins;387
17.3;III . Antithrombin;392
17.4;IV . Heparin Cofactor II;398
17.5;V . The Others;401
17.6;VI . Conclusions;407
18;Chapter 14. Role of Heparan Sulfate in Fibroblast Growth Factor Signaling ;418
18.1;I . Introduction and Perspective;418
18.2;II . Fibroblast Growth Factors;419
18.3;III . FGF receptors;421
18.4;IV.Interactions of the FGFs and FGFRs with Heparin;424
18.5;V. Structural Studies of FGF, FGFR and Heparin Complexes;433
18.6;VI. Conclusions and Future Perspectives;445
19;Chapter 15. Role of Anticoagulant Heparan Sulfate in Mammalian Reproduction;454
19.1;I. Introduction.;454
19.2;II. Anticoagulant Heparan Sulfate Proteogly;454
19.3;III. Anticoagulant Heparan Sulfate Proteoglycans in the Reproductive Tract;456
19.4;IV. Reproduction in Mice Deficient in Anticoagulant Heparan Sulfate Proteoglycans;470
19.5;V. Perspectives.;472
20;Chapter 16. Glycol-Splitting as a Device for Modulating Inhibition of Growth Factors and Heparanase by Heparin and Heparin Derivatives;480
20.1;I. Introduction.;480
20.2;II. Glycol-Split Heparins;481
20.3;III. Protein-Binding and Associated Biological Properties of Glycol-Split Heparins;486
20.4;IV. Conformational Implications of Glycol- Splitting ;493
20.5;V. Conclusions;495
21;Chapter 17. Antithrombin Activation and Designing Novel Heparin Mimics;502
21.1;I. Introduction;502
21.2;II. Antithrombin Inhibition of Procoagulant Proteinases;505
21.3;III. Structure of Heparin and Heparin Pentasaccharide ;506
21.4;IV. Mechanism of Heparin Activation of Antithrombin;507
21.5;V. The Heparin Binding Site in Antithrombin;510
21.6;VI. The Heparin Binding Site in Factor xa and Thrombin;512
21.7;VII. Thermodynamics and kinetics of Heparin Binding to Antithrombin ;513
21.8;VIII. Rationale for Designing Functrional Mimics of Heparin ;515
21.9;IX. Heparin Mimics;516
21.10;X. Conclusions;523
22;Chapter 18. Influence of Heparin Chemical Modifications on Its Antiproliferative Properties.;532
22.1;I. Introduction;532
22.2;II. Background and Significance of Chemical Modification of Heparin;533
22.3;III. Mechanisms Contributing to Heparin Inhibition of Smooth Muscle Cell Growth;534
22.4;IV. Importance of 3-0-Sulfo Group on the Internal Glucosamine Residue of Pentasaccharide for Antiproliferative Activity;535
22.5;V. Minimal Heparin Oligosaccharide Size Necessary for Antiproliferative Activity;536
22.6;VI. Effect of Chemical Modification of Heparin on Its Antiproliferative Activity;538
22.7;VII. Effect of the Type of Serum on Antiproliferative Activity;543
22.8;VIII. Conclusions;547
23;Chapter 19. Mechanisms of Cell Growth Regulation by Heparin and Heparan Sulfate;552
23.1;I. Introduction.;552
23.2;II. Modulation of Growth Factor Action;553
23.3;III. Direct Regulation of Cell Growth;563
23.4;IV. Growth Control in Disease;565
23.5;V. Conclusions;572
24;Chapter 20. Heparin and Low Molecular Weight Heparin in Thrombosis and Inflammation: Emerging Link;590
24.1;I. Introduction;590
24.2;II. Emerging Links Between Thrombosis and Inflammation: Potential Role of Heparin;591
24.3;III. Heparin versus Low Molecular Weight Heparin;594
24.4;IV. Heparin as an Anti-Inflammatory Molecule: Potential Mechanisms;596
24.5;V. Conclusions;597
25;Chapter 21. Basic and Clinical Differences of Heparin and Low Molecular Weight Heparin Treatment;602
25.1;I. Introduction.;602
25.2;II. Unfractionated Heparin and Newer Anticoagulant and Antithrombotic Drugs;603
25.3;III. Low Molecular Weight Heparins and Their Impact on the Management of Thromnbotic and Vascular Disorders ;608
25.4;IV. Monitoring of Heparin and Low Molecular Weight Heparins.;613
25.5;V. Clinical Trials with Low Molecular Weight Heparins;616
25.6;VI. Generic Low Molecular Weight Heparins..;617
25.7;VII. American College of Chest Physicians Consensus Recommendations ;619
25.8;VIII. Summary;622
26;Chapter 22. Perlecan: An Extracellular Matrix Heparan Sulfate Proteoglycan that Regulates Key Events in Vascular Development and Disease ;626
26.1;I. Introduction.;626
26.2;II. Perlecan-The Gene, the Protein Core, and the Glycosaminoglycans ;626
26.3;III. Perlecan is a Key Extracellular Matrix Component in Basement Membranes and in the Development of the Vascular System ;629
26.4;IV. Phenotypic Regulation of Vascular Cells by Perlecan;630
26.5;V.Perlecan in Intimal Hyperplasia;634
26.6;VI. Perlecan in Atherosclerosis;637
26.7;VII. Perlecan and Angiogenesis;640
26.8;VIII. Conclusions;642
27;Chapter 23. Heparin and Low Molecular Weight Heparins in Clinical Cardiology;656
27.1;I. Introduction ;656
27.2;II.Overview of Pharmacology;656
27.3;III. Clinical Experience;660
27.4;IV. Conclusions;681
28;Chapter 24. Heparin-Induced Thrombocytopenia;692
28.1;I. Introduction;692
28.2;II. Pathogenesis;692
28.3;III. Clinical Picture;696
28.4;IV. Laboratory Testing for Heparin-Induced Thrombocytopenia Antibodies;698
28.5;V. Treatment ;699
29;Chapter 25. Role of Heparan Sulfate in Cancer..;718
29.1;I. Introduction.;718
29.2;II. Structure Features of Glycosaminoglycans ;718
29.3;III. Biosynthesis and Degradation of Heparan Sulfate Glycosaminoglycans ;721
29.4;IV. Biological Functions of Heparan Sulfate Glycosaminoglycans ;722
29.5;V. Heparan Sulfate Glycosaminoglycans in Cancer ;725
30;Chapter 26. Use of Heparin Preparations in Older Patients;746
30.1;I. Introduction..;746
30.2;II. Aging and the Haemostatic System;747
30.3;III. Unfractionated Heparin, Low Molecular Weight Heparins, and Fondaparinux: Pharmacological Properties;748
30.4;IV. Unfractionated Heparin, Low Molecular Weight Heparins, and Fondaparinux: Clinical Use in Elderly;750
30.5;V. Heparin and Low Molecular Weight Heparins: Risk of Bleeding in the Elderly;753
30.6;VI. Conclusions and Perspectives ;756
31;Chapter 27. Advances in Low Molecular Weight Heparin Use in Pregnancy;764
31.1;I. Introduction;764
31.2;II. Pharmacology a Pharmacokinetics of Low Molecular Weight Heparin in Preganancy;764
31.3;III. Indications for the Use of Low Molecular Weight Heparin in Pregnancy;767
31.4;IV. Safety of Low Molecular Weight Heparin in Pregnancy;778
31.5;V. Conclusions;780
32;Subject Index;788