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The Design of Synthetic Inhibitors of Thrombin (in English)
Claeson, Goran ; Scully, Michael F. ; Kakkar, Vijay V. (Author)
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Springer
· Paperback
The Design of Synthetic Inhibitors of Thrombin (in English) - Claeson, Goran ; Scully, Michael F. ; Kakkar, Vijay V.
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Synopsis "The Design of Synthetic Inhibitors of Thrombin (in English)"
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.
