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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.
Recent years have seen tremendous advances in our understanding of
the molecular mechanism of platelet activation. All aspects of
signal transduction in platelets from the identification of surface
receptors, G proteins, phospholipases, protein kinases and
phosphatases, intracellular receptors for inositol phosphates, the
Ca2+ regulatory machinery, cytoskeletal constituents to the control
mechanism employing cyclic nucleotides has seen an explosion of
information regarding their importance and for each constituent in
the family of molecules to which they belong. This information has
been of interest to researchers across a wide spectrum of
disciplines including biochemists, pharmacologists, cell biologists
and clinicians. In April 1992 an International Symposium bearing
the name of this volume was organised at the Thrombosis Research
Institute to bring together scientists from across the world whose
common interest was the study of platelet activation and its
regulation. We were particularly encouraged by the positive
response from our speakers and the participants, their detailed
contributions and the very lively discussions that took place
throughout the two days of the symposium. Almost every aspect of
signal transduction in human platelets was represented. Of the
invited speakers twelve were from Europe (including the U. K. ),
eight from North America and one from Japan. This volume is a
compilation of chapters submitted by the speakers and represents a
concise but informative picture of the present knowledge of the
mechanisms of platelet activation and control.
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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