The Design of Synthetic Inhibitors of Thrombin
(Sprache: Englisch)
In one generation, the numerous factors involved in blood coagulation have become real protein entities, isolated in pure form, expressed by recombinant DNA techniques, and subjected to structure elucidation by the modem methods of physical chemistry, viz....
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In one generation, the numerous factors involved in blood coagulation have become real protein entities, isolated in pure form, expressed by recombinant DNA techniques, and subjected to structure elucidation by the modem methods of physical chemistry, viz. , X-ray diffraction, and NMR, ESR and fluorescence spectroscopy. The major milestone in this field was the breakthrough achieved by W. Bode, R. Huber and their colleagues in 1989 in of human a-thrombin, inhibited with D-Phe-Pro-Arg determining the crystal structure chioromethyl ketone. The availability of this structure will greatly facilitate the interpretation of experiments designed to gain an understanding of the interatomic interactions between this enzyme and fibrinogen and its other substrates. At the same time, it provides a rational basis for the design and synthesis of inhibitors of thrombin, the subject of this symposium. The symposium was organized in four sessions: (1) Structural features of the interaction of thrombin with substrates and inhibitors, (2) Synthetic inhibitors, (3) Hirudin and its analogues, and (4) Pharmacological and clinical considerations. This book contains summaries of most of the papers presented, and takes its rigbful place among two others that provide a comprehensive picture of our current knowledge about thrombin, viz. the 1977 volume entitled "Chemistry and Biology of Thrombin", edited by R. L. Lundblad, J. W. Fenton II, and K. G. Mann, and the 1992 volume entitled "Thrombin: Structure and Function", edited by L. J. Berliner.
Inhaltsverzeichnis zu „The Design of Synthetic Inhibitors of Thrombin “
The Rational Design of Thrombin-Directed Antithrombotics.- X-Ray Crystal Structures of Thrombin in Complex with D-Phe-Pro-Arg and with Small Benzamidine and Arginine-Based "Non-Peptidic" Inhibitors.- Inhibitor Binding to Thrombin: X-Ray Crystallographic Studies.- Molecular Basis for the Inhibition of Thrombin by Hirudin.- Biophysical Studies of Interactions of Hirudin Analogs with Bovine and Human Thrombin by ESR and Fluorescence Labelling Studies.- pH-Dependent Binding Constants for the Inhibition of Thrombin by Transition State Analogues.- The Comparison of an Interim Tertiary Predicted Model of Bovine Thrombin and the X-Ray Structure of Human Thrombin.- Design of Novel Types of Thrombin Inhibitors Based on Modified D-Phe-Pro-Arg sequences.- Chemistry and Biology of the Peptide Anticoagulant D-MePhe-Pro-Arg-H (GYKI-14766).- Peptide Boronic Acid Inhibitors of Thrombin.- In Vitro and In Vivo Properties of Synthetic Inhibitors of Thrombin: Recent Advances.- The Use of Isosteric Bonds in the Design of Thrombin Inhibitors.- Synthetic Thrombin Inhibitors as Anticoagulants Pharmacological Aspects.- New Peptide Boronic Acid Inhibitors of Thrombin.- Substrate-Related Phosphonopeptides as Thrombin Inhibitors.- The Synthesis and Anticoagulant Activity of Novel Peptidylfluoroalkanes.- Transition State Analogue Inhibitors of Thrombin: Synthesis Activity and Molecular Modelling.- Hirudin: The Famous Anticoagulant Agent.- Mechanisms for the Anticoagulant Effects of Synthetic Antithrombins.- Pre-Clinical and Clinical Studies on Hirulog: A Potent and Specific Direct Thrombin Inhibitor.- The Effect of Recombinant Hirudin on Arterial Thrombosis.
Bibliographische Angaben
- 1993, 260 Seiten, Maße: 18,3 x 26 cm, Gebunden, Englisch
- Herausgegeben: Goran Claeson, John Deadman, Vijay V. Kakkar, Michael F. Scully
- Verlag: Springer US
- ISBN-10: 030644593X
- ISBN-13: 9780306445934
- Erscheinungsdatum: 31.01.1994
Sprache:
Englisch
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