RGDS AND LGGAKQAGDV BINDING SITES ON GPIIB/IIIA

这个项目的目标是鉴定氨基酸 纤维蛋白原受体区域(S)的序列(S) 糖蛋白IIb/IIIa复合体)与相应的多肽结合 分别为α的RGDS和LGGAKQAGDV序列 和FG的Gamma链。这将通过使用 分子识别假说与基因序列信息 人类纤维蛋白原的阿尔法链和伽马链。这 信息将被用于指导多肽的合成，这些多肽 是猪纤维蛋白原结合区(S)的假定类似物 它的受体。这些推定的多肽类似物 纤维蛋白原受体有望与 RGDS和LGGAKQAGDV能够结合 纤维蛋白原。这一预期将通过确定是否 这些多肽可以抑制血小板聚集、纤维蛋白原结合 以及凝块回缩。还将对活性多肽进行表征 采用亲和层析和平衡透析法。免疫学 技术将被用来确定假定的纤维蛋白原 受体类似物具有存在于血小板上的表位 纤维蛋白原受体。这种方法将扩展到另一种方法 可与GPIIb/IIIa复合体结合的粘附性糖蛋白： 纤维连接蛋白、玻璃体连接蛋白和血管性血友病因子。鉴定 纤维蛋白原受体的配体结合区(S)将 增加我们对血小板功能的了解，从而提供 有助于控制血栓性疾病的信息。 具体地说，对多肽类似物的表征 纤维蛋白原受体抑制血小板聚集、凝块 回缩和纤维蛋白原结合可能提供了一个理论基础 临床有用的抗血栓药物的设计。

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.