Mohri H, Ohkubo T
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Peptides. 1993 Mar-Apr;14(2):353-7. doi: 10.1016/0196-9781(93)90052-i.
The interaction of fibrinogen with platelet membrane glycoprotein (GP) IIb/IIIa complex is inhibited by the RGD peptides and the peptides corresponding to a sequence unique to fibrinogen in the carboxyl-terminal domain of the gamma chain. The present study was designed to examine the effects of these synthetic peptides on fibrinogen binding to thrombin-activated platelets. The order of potency of these peptides was as follows: RGDS = RGDF > GQQHHLGGAKQAGDV (G15). The RGES peptide had no inhibitory activity. The inhibitory effects of the peptides were synergistic when fibrinogen binding was measured in the mixture of the RGD peptide and the gamma chain peptide. By contrast, the inhibitory effect was additive when the binding was measured in the presence of the RGDS peptide and the RGDF peptide. Thrombin-induced platelet aggregation was also inhibited by these synthetic peptides. The order of potency was the same as that of the inhibition binding assay. These results provide evidence that the RGD sequences present at two different sites in the alpha chain and the gamma chain sequence inhibit fibrinogen binding to the GPIIb/IIIa complex, are mutually exclusive, and are in close spatial proximity in the folded molecule. We conclude that the presence of the RGD sequence and the gamma chain sequence involved in fibrinogen binding domains increases the affinity of fibrinogen to activated platelets.
纤维蛋白原与血小板膜糖蛋白（GP）IIb/IIIa复合物的相互作用受到RGD肽以及与γ链羧基末端结构域中纤维蛋白原独特序列相对应的肽的抑制。本研究旨在检测这些合成肽对纤维蛋白原与凝血酶激活血小板结合的影响。这些肽的效力顺序如下：RGDS = RGDF > GQQHHLGGAKQAGDV（G15）。RGES肽没有抑制活性。当在RGD肽和γ链肽的混合物中测量纤维蛋白原结合时，这些肽的抑制作用具有协同性。相比之下，当在RGDS肽和RGDF肽存在的情况下测量结合时，抑制作用是相加的。这些合成肽也抑制凝血酶诱导的血小板聚集。效力顺序与抑制结合试验相同。这些结果提供了证据，表明存在于α链和γ链序列中两个不同位点的RGD序列抑制纤维蛋白原与GPIIb/IIIa复合物的结合，它们相互排斥，并且在折叠分子中空间距离很近。我们得出结论，参与纤维蛋白原结合结构域的RGD序列和γ链序列的存在增加了纤维蛋白原对活化血小板的亲和力。
