合成肽可抑制血管性血友病因子与血小板膜糖蛋白的相互作用。

Synthetic peptides inhibit the interaction of von Willebrand factor-platelet membrane glycoproteins.

作者信息

Mohri H, Zimmerman T S, Ruggeri Z M

机构信息

First Department of International Medicine, Yokohama City University School of Medicine, Japan.

出版信息

Peptides. 1993 Mar-Apr;14(2):125-9. doi: 10.1016/0196-9781(93)90019-d.

DOI:10.1016/0196-9781(93)90019-d

PMID:8483792

Abstract

We synthesized peptides of the general formula Argn, Lysn, and (Lys-Arg)n. These agents inhibited the ristocetin-mediated binding of vWF to GPIb and the binding of asialo-vWF to platelets. This inhibitory activity was proportional to the number of lysine and/or arginine residues/molecules present. Peptides to which the sequence of Arg-Gly-Asp-Val (RGDV) had been added at the carboxy-terminus of (Lys-Arg)n, Lysn, or Argn also inhibited vWF binding. Peptides with an RGDV sequence were found to block the binding of 125I-fibrinogen to ADP-stimulated platelets. These findings indicate that the general formulae (Lys-Arg)n, Lysn, and Argn with an RGDV sequence inhibit the binding of fibrinogen to activated platelets as well as the binding of vWF to GPIb. Thus, these peptides may behave as bifunctional antiplatelet agents.

摘要

我们合成了通式为Argn、Lysn和(Lys-Arg)n的肽。这些试剂抑制瑞斯托菌素介导的血管性血友病因子（vWF）与糖蛋白Ib（GPIb）的结合以及去唾液酸vWF与血小板的结合。这种抑制活性与存在的赖氨酸和/或精氨酸残基/分子数量成正比。在(Lys-Arg)n、Lysn或Argn的羧基末端添加了精氨酸-甘氨酸-天冬氨酸-缬氨酸（RGDV）序列的肽也抑制vWF结合。发现具有RGDV序列的肽可阻断125I-纤维蛋白原与二磷酸腺苷（ADP）刺激的血小板的结合。这些发现表明，具有RGDV序列的通式(Lys-Arg)n、Lysn和Argn抑制纤维蛋白原与活化血小板的结合以及vWF与GPIb的结合。因此，这些肽可能表现为双功能抗血小板剂。