PLATELET-FIBRINOGEN INTERACTIONS

纤维蛋白原在血小板聚集中起重要作用。 血小板活化后，纤维蛋白原与钙离子结合， 血小板膜糖蛋白依赖性复合物Ⅱ b 和Ilia。 已经提出，具有二聚体的纤维蛋白原， 结构和双重对称，可以作为一个桥梁， 相邻血小板中存在两个GP IIb-IIIa复合物。 至少有两个好- 在纤维蛋白原中定义的序列，在N- γ链末端部分和Arg-Gly-Asp序列 A α链（A α 95-97和/或A α 574-576）是 显示与血小板GP IIb-IIIa相互作用。 我们最近 显示了衍生自氨基的合成肽B β 15-42， B β链末端，抑制ADP和凝血酶诱导的 血小板聚集呈剂量依赖性。 此外，委员会认为， 在结合研究中，该肽抑制125 I-纤维蛋白原与 激活血小板 这种肽在体内由 凝血酶和纤溶酶对纤维蛋白（原）的联合作用， 在外周血中检测到。 这项建议的目的是 为了进一步确定所需的最小氨基酸序列， 这种效应，以确定这种肽的作用是否 通过与Gp IIb-IIIa或与 纤维蛋白原，并确定这种肽对纤维蛋白原的影响。 其他粘附糖蛋白与GP IIb-IIIa的相互作用。 在 此外，将通过以下方法制备缺乏B β 15-42的纤维蛋白原： 用来自响尾蛇毒液的蛋白酶III切割， 这种纤维蛋白原对血小板聚集作用将是 测定 这些研究将阐明 血小板纤维蛋白原中B β链氨基末端 交互.

Fibrinogen plays an essential role in platelet aggregation. Following platelet activation, fibrinogen binds to a calcium- dependent complex of platelet membrane glycoproteins (Gp) IIb and IIIa. It has been proposed that fibrinogen, with a dimeric structure and two-fold symmetry, may act as a bridge between two Gp IIb-IIIa complex in adjacent platelets. At least two well- defined sequences in fibrinogen, the gamma-400-411 in the N- terminal part of gamma chain and the Arg-Gly-Asp sequences in the A alpha chain (A alpha 95-97 and/or A alpha 574-576) are shown to interact with platelet Gp IIb-IIIa. We have recently shown that the synthetic peptide B beta 15-42 derived from amino terminal end of B beta chain, inhibits ADP and thrombin-induced platelet aggregation in a dose-dependent manner. Furthermore, in binding studies this peptide inhibits 125I-fibrinogen binding to activated platelets. This peptide is generated in vivo by the combined actions of thrombin and plasmin on fibrin(ogen) and has been detected in peripheral blood. The aims of this proposal are to further define the minimal aminoacid sequence required for this effect, to determine whether the effect of this peptide is mediated through its interaction with Gp IIb-IIIa or with fibrinogen, and to determine the effect of this peptide on the interaction of other adhesive glycoproteins to Gp IIb-IIIa. In addition, fibrinogen lacking B beta 15-42 will be prepared by cleavage with Protease III from Crotalus atrox venom and the effect of this fibrinogen on platelet aggregation will be determined. These studies will elucidate the importance of aminoterminal end of B beta chain in platelet-fibrinogen interactions.