PEPTIDE MIMICS OF THE FG RECEPTOR LIGAND BINDING SITES

描述：（改编自研究者摘要）。 的目标 该项目是表征肽模拟物的区域（S）的 纤维蛋白原（Fg）受体，其结合对应于RGDX的肽 Fg、纤连蛋白（Fn）、玻连蛋白（Vn）和血管性血友病因子（von Willebrand）的序列 Fg的γ-链的LGGAKQAGDV序列， 了解Fg与其受体的相互作用， 为设计一种新的局部或系统性的， 血小板特异性抗血栓剂。 这一目标将是 通过使用分子识别假说和cDNA完成 人Fg、Fn、Vn和vWF的信息。 此信息将用于 指导肽的合成，所述肽是所述肽的假定模拟物。 Fg受体的纤维蛋白原结合区。 这些假定 预期Fg受体的肽模拟物与Fg受体互补。 肽RGDS和LGGAKQAGDV，因此能够结合Fg。这 预期将通过确定这些肽是否可以结合Fg来测试。 ELISA。 将对所有肽进行分析，以确定它们是否可以 抑制血小板聚集、Fg与血小板结合和血块收缩。 活性肽也将通过亲和色谱法表征， 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Fg受体或其它血小板质膜蛋白。 的 活性肽将作为成纤维细胞附着的抑制剂进行测试， Tn测定，并作为两栖动物胚胎发育的调节剂。 的 活性肽也将作为抗血栓形成剂进行测试， 人造管道和人类脐带动脉。 表征 这些肽可以为设计一类新的 抗血栓形成剂：与Fg结合而不是与Fg竞争的肽 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.