FUNCTION OF THE PLATELET LECTIN (TSP) IN AGGREGATION

本项目的长期目标是阐明 这些事件是人血小板的分泌依赖性聚集的基础。 这里提出的实验的直接目标是阐明 内源性血小板凝集素（其是糖蛋白， 血小板反应蛋白）在血小板分泌依赖性聚集中的作用 （血小板反应蛋白由α-颗粒分泌）。 这一目标将 通过使用生物化学，化学和免疫学的组合来实现 技术来识别这些区域（每个区域仅由相邻的 血小板反应蛋白（内源性血小板凝集素）的氨基酸序列 其在血小板聚集中起关键作用。 这项工作应 导致短肽的合成（每一个由连续的 血小板反应蛋白中发现的氨基酸序列），其可用作工具 为了阐明分泌依赖性聚集的分子细节， 血小板 这些肽也能够控制 “不可逆”血小板聚集。 因此，这些肽可以提供抗肿瘤活性。 设计具有预防和/或治疗作用的肽的基本原理 对有血栓形成倾向的患者的价值。

The long term objective of this project is to elucidate the molecular events which underlie secretion-dependent aggregation of human platelets. The immediate goal of the experiments proposed here are to clarify the role of the endogenous platelet lectin (which is the glycoprotein, thrombospondin) in the secretion-dependent aggregation of platelets (thrombospondin is secreted from alpha-granules). This goal will be attained by using a combination of biochemical, chemical and immunological techniques to identify those regions (each composed only of a contiguous sequence of amino acids) of thrombospondin (the endogenous platelet lectin) which play a critical role(s) in platelet aggregation. This work should result in the synthesis of short peptides (each composed of a contiguous sequence of amino acids found in thrombospondin) which can be used as tools for elucidating the molecular details of secretion-dependent aggregation of platelets. These peptides may also be capable of controlling "irreversible" platelet aggregation. Thus, these peptides may provide a rationale for designing peptides that have prophylactic and/or therapeutic value for patients with thrombotic tendencies.