CHEMICAL AND STRUCTURAL STUDIES ON FACTOR VIII/VON WILLEBRAND FACTOR PROTEIN

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The long-range purpose of this project is to study the immunologic, biochemical, and molecular genetic aspects of von Willebrand factor (vWf) protein. We have initiated studies to identify fragments of vWf that can act as antithrombotic agents. These vWf fragments are in the Val449-Ser728 region of the plasma protein. Identification of a recombinant fragment of vWf Met504-Lys728 inhibits plasma and platelet vWf binding to GPIb, heparin, and GBIIb/IIla. Topics of present interest are (1) the defects of the vWf protein in von Willebrand's disease; (2) the importance of carbohydrate content in biological functions; (3) the relationship of carbohydrate content to atherosclerosis; (4) the mechanism(s) of thrombin activation; and (5) biochemical characterization of the biologically active sites of the factor VIII/vWf proteins. Recent studies of the platelet vWf isolated from human platelets reveal significant differences from its plasma counterpart.