STRUCTURE-FUNCTION STUDIES OF FIBRINOGEN

纤维蛋白原的结构功能研究

• 批准号: 3351095
• 负责人: WILLIAM R JR BELL
• 金额: $ 16.53万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3351095
• 关键词: anticoagulants; binding proteins; blood coagulation disorders; chemical binding; enzyme mechanism; fibrin; fibrinogen; fibrinolysis; gel electrophoresis; high performance liquid chromatography; laboratory mouse; light scattering; monoclonal antibody; peptides; polymerization; protein metabolism; protein sequence; protein structure function; thrombin

The long term objective of the proposed study is to obtain an improved understanding of blood coagulation mechanisms and to develop new approaches to anticoagulant and thrombolytic therapy. Functionally important domains in fibrinogen will be identified by determining the structural defects in seven dysfibrinogens. A systematic and general technique, comparative peptide mapping by high-performance liquid chromatography, will be used to locate these structural defects. As each molecular defect is identified,, peptides corresponding to and monoclonal antibodies directed against newly identified functional domains will be used as probes to study the fibrinogen- to-fibrin conversion. In addition, the fibrin(ogen) binding sites of monoclonal antibodies which inhibit coagulation (supplied by consultant B. Kudryk) will be determined. Emphasis will be placed on correlating structure with function. The information derived from these studies will provide a rational basis for (1) design of peptide anticoagulants, (ii) design of targeted thrombolytic agents, and (iii) an improved methodology for determining the structural defects in other dysfibrinogens or mutant proteins.

建议研究的长远目标是 提高对凝血机制的认识， 开发抗凝和溶栓的新方法 疗法 纤维蛋白原中功能重要的结构域将通过 确定七种纤维蛋白原异常的结构缺陷。 一 系统和通用技术，比较肽图谱 通过高效液相色谱法，将用于定位 这些结构性缺陷。 当每个分子缺陷被鉴定时， 和针对新发现的 功能结构域将被用作探针来研究纤维蛋白原， 纤维蛋白转化。 此外，纤维蛋白（原）结合位点 抑制凝血的单克隆抗体（由 顾问B。”郭文贵信誓旦旦。 重点将 把结构和功能联系起来。 从这些研究中获得的信息将提供一个合理的 （1）肽抗凝剂的设计，（ii） 靶向血栓溶解剂，和（iii）改进的方法 用于确定其他纤维蛋白原异常的结构缺陷，或 突变蛋白