VON WILLEBRAND FACTOR AND PLATELET-MEDIATED HEMOSTASIS

血管性血友病因子和血小板介导的止血

• 批准号: 3339401
• 负责人: EDWARD P KIRBY
• 金额: $ 17.72万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-05-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3339401
• 关键词: binding proteins; chemical binding; chemical models; circular dichroism; collagen; complementary DNA; cow; endopeptidases; glycoproteins; hemostasis; human tissue; ligands; membrane proteins; monoclonal antibody; platelets; protein sequence; protein structure function; proteoglycan; receptor; synthetic peptide; vascular endothelium; von Willebrand factor

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.

描述：（根据调查员的摘要进行了改编） 项目是：（a）识别VWF分子的区域 负责与血小板，胶原蛋白和 蛋白聚糖； （b）确定这些结构的3维结构 结合域； （c）表征分子机制 负责将VWF与其配体结合。 功能域 VWF分子将通过蛋白水解鉴定和表征 VWF的分裂，通过化学和酶促修饰VWF的碎片化， 通过使用抑制特定功能的单克隆抗体 vwf。 这些碎片的结构将通过准备和 通过片段的氨基酸测序对牛VWF进行测序， 并通过对这些碎片的物理研究。 互补域 VWF的血小板受体也将通过蛋白水解制备 血小板膜糖蛋白IB的碎片。机制 相互作用将通过制备合成肽类似物来定义 结合域并检查它们与VWF和糖蛋白IB的结合。