Trigramin. A low molecular weight peptide inhibiting fibrinogen interaction with platelet receptors expressed on glycoprotein IIb-IIIa complex.
Trigramin. A low molecular weight peptide inhibiting fibrinogen interaction with platelet receptors expressed on glycoprotein IIb-IIIa complex.
复制标题
DOI：
10.1016/s0021-9258(18)47710-1
复制
发表时间：
1987-11
期刊：
影响因子：
--
通讯作者：
Tur F. Huang;J. Holt;H. Lukasiewicz;S. Niewiarowski
中科院分区：
文献类型：
--
作者：
Tur F. Huang;J. Holt;H. Lukasiewicz;S. Niewiarowski
从竹叶青蛇蛇毒中分离纯化出一种高度特异性的纤维蛋白原血小板受体抑制剂--曲明。Trigramin是具有Glu-Ala-Gly-Glu-Asp-Cys-Asp-Cys-Gly-Ser-Pro-Ala NH 2-末端序列的单链（约9 kDa）富含半胱氨酸的肽。胰凝乳蛋白酶片段化显示了trigramin的Arg-Gly-Asp序列。Trigramin可抑制ADP诱导的血小板聚集（IC_（50）= 1.3 × 10 ~（-7）M）和糜蛋白酶处理的血小板聚集。对血小板分泌无影响。Trigramin对ADP刺激的血小板与~（125）I-纤维蛋白原的结合有竞争性抑制作用（Ki = 2 × 10（-8）M）。125 I-Trigramin以饱和方式与静息血小板（Kd = 1.7 × 10（-7）M; n = 16，500）、ADP刺激的血小板（Kd = 2.1 × 10（-8）M; n = 17，600）和胰凝乳蛋白酶处理的血小板（Kd = 8.8 × 10（-8）M; n = 13，800）结合。125 I-trigramin结合位点的数量thrombasthenic血小板相当于正常血小板获得的对照值的2.7-5.4%，并与血小板表面上GPIIb-GPIIIa分子的数量减少相关。EDTA、针对GPIIb-GPIIIa复合物的单克隆抗体和合成肽（Arg-Gly-Asp-Ser和Tyr-Gly-Gln-Gln-His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val）阻断125 I-纤维蛋白原结合和125 I-trigramin与血小板的结合。纤维蛋白原结合更容易抑制这些化合物比曲明结合。针对GPIIb或GPIIIa分子的单克隆抗体不阻断任一配体与血小板的相互作用。还原的S-吡啶基乙基曲格明不抑制血小板聚集和纤维蛋白原与血小板的结合，并且它不与血小板结合，这表明该分子的二级结构对于其生物活性的表达是至关重要的。
Trigramin, a highly specific inhibitor of fibrinogen binding to platelet receptors, was purified to homogeneity from Trimeresurus gramineus snake venom. Trigramin is a single chain (approximately 9 kDa) cysteine-rich peptide with the Glu-Ala-Gly-Glu-Asp-Cys-Asp-Cys-Gly-Ser-Pro-Ala NH2-terminal sequence. Chymotryptic fragmentation showed the Arg-Gly-Asp sequence in trigramin. Trigramin inhibited fibrinogen-induced aggregation of platelets stimulated by ADP (IC50 = 1.3 × 10(-7)M) and aggregation of chymotrypsin-treated platelets. It did not affect the platelet secretion. Trigramin was a competitive inhibitor of the 125I-fibrinogen binding to ADP-stimulated platelets (Ki = 2 × 10(-8) M). 125I-Trigramin bound to resting platelets (Kd = 1.7 × 10(-7) M; n = 16,500), to ADP-stimulated platelets (Kd = 2.1 × 10(-8) M; n = 17,600), and to chymotrypsin-treated platelets (Kd = 8.8 × 10(-8) M; n = 13,800) in a saturable manner. The number of 125I-trigramin binding sites on thrombasthenic platelets amounted to 2.7-5.4% of control values obtained for normal platelets and correlated with the reduced number of GPIIb-GPIIIa molecules on the platelet surface. EDTA, monoclonal antibodies directed against the GPIIb-GPIIIa complex, and synthetic peptides (Arg-Gly-Asp-Ser and Tyr-Gly-Gln-Gln-His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val) blocked both 125I-fibrinogen binding and 125I-trigramin binding to platelets. Fibrinogen binding was more readily inhibited by these compounds than was trigramin binding. Monoclonal antibodies directed either against GPIIb or GPIIIa molecules did not block the interaction of either ligand with platelets. Reduced, S-pyridylethyl, trigramin did not inhibit platelet aggregation and fibrinogen binding to platelets and it did not bind to platelets, suggesting that the secondary structure of this molecule is critical for expression of its biological activity.