The goals of this project are: (a) to identify the regions of the vWF molecule which are responsible for its binding to platelets, to collagen, and to proteoglycans; (b) to determine the 3-dimensional structure of these binding domains; and (c) to characterize the molecular mechanism responsible for binding of vWF to its ligands. Functional domains on the vWF molecule will be identified and characterized by proteolytic fragmentation of the vWF, by chemical and enzymatic modification of vWF, and by use of monoclonal antibodies which inhibit specific functions of vWF. The structure of these fragments will be determined by preparing and sequencing the cDNA for bovine vWF, by amino acid sequencing of fragments, and by physical studies of these fragments. Complementary domains on the platelet receptor for vWF will also be prepared by proteolytic fragmentation of platelet membrane glycoprotein Ib. Mechanisms of interaction will be defined by preparation of synthetic peptide analogs of binding domains and examining their binding to vWF and glycoprotein Ib.
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