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The Design of Synthetic Inhibitors of Thrombin (Hardcover, 1993 ed.)
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The Design of Synthetic Inhibitors of Thrombin (Hardcover, 1993 ed.)
Series: Advances in Experimental Medicine and Biology, 340
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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.
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