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RGDS AND LGGAKQAGDV BINDING SITES ON GPIIB/IIIA

GPIIB/IIIA 上的 RGDS 和 LGGAKQAGDV 结合位点

基本信息

批准号：
3440100
负责人：
T. KENT GARTNER
金额：
$ 9.99万
依托单位：
UNIVERSITY OF MEMPHIS
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-04-15 至 1991-03-31
项目状态：
已结题

项目摘要

The objective of this project is to identify the amino acid sequence(s) of the region(s) of the fibrinogen receptor (the glycoprotein IIb/IIIa complex) which bind peptides corresponding to the RGDS and LGGAKQAGDV sequences, respectively, of the alpha and gamma-chains of Fg. This will be accomplished by using the molecular recognition hypothesis and the cDNA sequence information for the alpha and gamma-chains of human fibrinogen. This information will be used to direct the synthesis of peptides which are presumptive analogues of the fibrinogen binding region(s) of its receptors. These presumptive peptide analogues of the fibrinogen receptor are expected to be complementary with the peptides RGDS and LGGAKQAGDV and therefore be able to bind fibrinogen. This expectation will be tested by determining if these peptides can inhibit platelet aggregation, fibrinogen binding and clot retraction. Active peptides will also be characterized by affinity chromatography and equilibrium dialysis. Immunological techniques will be used to determine if the presumptive fibrinogen receptor analogues have epitopes which are present on platelet fibrinogen receptors. This approach will be extended to the other adhesive glycoproteins which can bind to GPIIb/IIIa complexes: fibronectin, vitronectin and von Willebrand factor. Identification of the ligand binding region(s) of the fibrinogen receptors will increase our understanding of platelet function and thereby provide information useful for the control of thrombotic disease. Specifically, characterization of the peptide analogues of the fibrinogen receptors which inhibit platelet aggregation, clot retraction and fibrinogen binding may provide a rationale for the design of clinically useful anti-thrombotic agents.

本项目的目标是鉴定氨基酸纤维蛋白原受体（纤维蛋白原受体）区域的序列糖蛋白IIb/IIIa复合物），其结合相应的肽分别与α-葡聚糖酶的RGDS和LGGAKQAGDV序列连接，和Fg的γ-链。这将通过使用分子识别假说和cDNA序列信息人纤维蛋白原的α和γ链这这些信息将用于指导肽的合成，是纤维蛋白原结合区的假定类似物，它的受体。这些推定的肽类似物的纤维蛋白原受体预期与肽RGDS和LGGAKQAGDV，因此能够结合纤维蛋白原。这一预期将通过确定是否这些肽可以抑制血小板聚集、纤维蛋白原结合和血块收缩活性肽也将被表征通过亲和层析和平衡透析。免疫技术将被用来确定是否假定纤维蛋白原受体类似物具有存在于血小板上的表位纤维蛋白原受体这种方法将推广到其他可与GPIIb/IIIa复合物结合的粘附性糖蛋白：纤维连接蛋白、玻连蛋白和血管性血友病因子。识别纤维蛋白原受体的配体结合区的一部分将增加我们对血小板功能的了解，从而提供对血栓性疾病的控制有用的信息。具体地，本发明的肽类似物的表征包括以下步骤：纤维蛋白原受体抑制血小板聚集、凝块收缩和纤维蛋白原结合可能为设计临床上有用的抗血栓药物。