PEPTIDE MIMICS OF THE FG RECEPTOR LIGAND BINDING SITES

描述：(改编自调查人员摘要)。的目标是 本项目是为了表征多肽模拟物的区域(S) 与RGDX对应的多肽结合的纤维蛋白原(FG)受体 Fg、纤维连接蛋白(Fn)、玻璃体连接蛋白(Vn)和von Willebrand的序列 因子(VWF)和FG的伽马链的LGGAKQAGDV序列 了解纤维蛋白原与其受体的相互作用 为设计一类新的局部或系统的 血小板特异性抗血栓药。这一目标将是 通过使用分子识别假说和cDNA. 人类FG、FN、VN和vWF的信息。这些信息将被用于 指导多肽的合成，这些多肽是假定的模拟 FG受体的纤维蛋白原结合区(S)。这些假定 FG受体的多肽模拟物有望与 因此，RGDS和LGGAKQAGDV能够与FG结合。这 通过确定这些多肽是否能结合FG来测试期望值 一份ELISA卡。所有的多肽都将被检测，以确定它们是否可以 抑制血小板聚集、纤维蛋白原与血小板结合和凝块回缩。 活性多肽还将通过亲和层析和 平衡透析。将使用免疫学技术来确定 如果假定的FG受体模拟物具有存在于 血小板膜Fg受体或其他血小板质膜蛋白。这个 活性多肽将作为抑制物在成纤维细胞与 TN测定，并作为两栖类胚胎发育的调节因子。这个 活性多肽也将被测试为抗血栓药物，使用 人工管道和人脐动脉。特征描述 这些多肽可能为设计一类新的 抗血栓药：与纤维蛋白原结合而不是竞争的多肽 Fg用于与其受体结合。

DESCRIPTION: (Adapted from investigator's abstract). The objective of this project is to characterize peptide mimics of the region(s) of the fibrinogen(Fg) receptor which bind peptides corresponding to the RGDX sequences of Fg, fibronectin(Fn), vitronectin(Vn) and von Willebrand factor(vWF) and the LGGAKQAGDV sequence of the gamma-chain of Fg for the purposes of understanding the interaction of Fg with its receptor and to provide a rationale for designing a new class of local, or systemic, platelet specific antithrombotic agents. This objective will be accomplished by using the molecular recognition hypothesis and the cDNA information for human Fg, Fn, Vn and vWF. This information will be used to direct the synthesis of peptides which are presumptive mimics of the fibrinogen binding region(s) of the Fg receptors. These presumptive peptide mimics of the Fg receptor are expected to be complementary with the peptides RGDS and LGGAKQAGDV and therefore, be able to bind Fg. This expectation will be tested by determining if these peptides can bind Fg in an ELISA. All of the peptides will be assayed to determine if they can inhibit platelet aggregation, Fg binding to platelets 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 Fg receptor mimics have epitopes which are present on platelet Fg receptors, or other platelet plasma membrane proteins. The active peptides will be tested as inhibitors in a fibroblast attachment to Tn assay, and as modulators of development of amphibian embryos. The active peptides will also be tested as antithrombotic agents using artificial conduits and human umbilical cord arteries. Characterization of these peptides may provide a rationale for the design of a new class of antithrombotic agents: peptides which bind to Fg rather than compete with Fg for binding to its receptor.