VON WILLEBRAND FACTOR AND PLATELET-MEDIATED HEMOSTASIS

描述：(改编自调查人员摘要)这项计划的目标 项目是：(A)确定vWF分子的哪些区域 负责它与血小板、胶原蛋白的结合，以及 蛋白多糖；(B)确定这些蛋白多糖的三维结构 结合结构域；和(C)表征分子机制 负责vWF与其配体的结合。上的功能域 VWF分子将通过蛋白水解法进行鉴定和表征 通过对vWF进行化学和酶修饰来裂解vWF， 并通过使用抑制特定功能的单抗 VWF。这些片段的结构将通过制备和 对牛vWF的cDNA进行测序，通过片段的氨基酸测序， 通过对这些碎片的物理研究。上的互补域 VWF的血小板受体也将通过蛋白水解法制备 血小板膜糖蛋白Ib的碎裂。机制： 相互作用将通过制备合成的多肽类似物来定义 结合结构域并检测其与vWF和糖蛋白Ib的结合。

DESCRIPTION: (Adapted from investigator's abstract) 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.