THE EFFECT OF ARG-GLY-ASP-CONTAINING PEPTIDES ON FIBRINOGEN AND VON WILLEBRAND FACTOR BINDING TO PLATELETS
THE EFFECT OF ARG-GLY-ASP-CONTAINING PEPTIDES ON FIBRINOGEN AND VON WILLEBRAND FACTOR BINDING TO PLATELETS
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DOI：
10.1073/pnas.82.23.8057
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
GINSBERG, MH
中科院分区：
文献类型：
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作者：
PLOW, EF;PIERSCHBACHER, MD;GINSBERG, MH
Arg-Gly-Asp 序列位于纤连蛋白的细胞附着区域。含有精氨酸-甘氨酸-天冬氨酸的肽支持成纤维细胞附着，抑制成纤维细胞与纤连蛋白的粘附，并抑制纤连蛋白与凝血酶刺激的血小板的结合。鉴于纤连蛋白、纤维蛋白原和血管性血友病因子与受刺激血小板的结合之间的相似性，我们研究了含精氨酸-甘氨酸-天冬氨酸的肽对后两种粘附蛋白与血小板相互作用的影响。 Gly-Arg-Gly-Asp-Ser-Pro用作原型肽，并且该六肽在10-200μM范围内抑制纤维蛋白原与ADP和凝血酶刺激的血小板的结合。在高浓度的肽下，抑制率超过 90%，并且在钙或镁存在的情况下观察到。在此剂量范围内的肽也抑制血小板聚集。六肽抑制纤维蛋白原与固定在暴露状态的受体的血小板结合，表明对配体-血小板相互作用的直接干扰。该肽抑制纤维蛋白原的效力是纤连蛋白与血小板结合的 1/2 至 1/3，但纤维蛋白原和血管性血友病因子结合的抑制程度相同。精氨酸、甘氨酸或天冬氨酸的保守氨基酸取代显着降低了抑制活性，并且 Asp-Gly-Arg 序列失去活性。这些结果表明，含有Arg-Gly-Asp的肽可以抑制三种粘附蛋白与刺激的血小板的结合，建立这些分子与血小板相互作用之间的基本共同特征。
The Arg-Gly-Asp sequence resides in the cell attachment region of fibronectin. Arg-Gly-Asp-containing peptides support fibroblast attachment, inhibit fibroblast adhesion to fibronectin, and inhibit fibronectin binding to thrombin-stimulated platelets. In view of the similarities between the binding of fibronectin, fibrinogen, and von Willebrand factor to stimulated platelets, we have examined the effects of Arg-Gly-Asp-containing peptides on the interaction of these latter two adhesive proteins with platelets. Gly-Arg-Gly-Asp-Ser-Pro was used as a prototype peptide, and this hexapeptide inhibited fibrinogen binding to ADP and thrombin-stimulated platelets in the 10-200 .mu.M range. The inhibition exceeded 90% at high concentrations of peptide and was observed in the presence of either calcium or magnesium. Platelet aggregation was also inhibited by the peptide in this dose range. The hexapeptide inhibited fibrinogen binding to platelets with receptors fixed in an exposed state, indicating direct interference with the ligand-platelet interaction. The peptide was 1/2 to 1/3rd as potent in inhibiting fibrinogen as fibronectin binding to platelets, but fibrinogen and von Willebrand factor binding were inhibited to an identical extent. Conservative amino acid substitutions for the arginine, glycine, or aspartic acid markedly reduced inhibitory activity and the Asp-Gly-Arg sequence was inactive. These results indicate that Arg-Gly-Asp-containing peptides can inhibit the binding of the three adhesive proteins to stimulated platelets, establishing a basic common feature between the interaction of these molecules with platelets.