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首页> 外文期刊>Cell communication & adhesion >The Effect fo the Single Substitution of Arginine within the RGd Tripeptide Mofif of a Modified Neurotoxin Dendroaspin on Its Activity of Platelet Aggregation and Cell Adhesion
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The Effect fo the Single Substitution of Arginine within the RGd Tripeptide Mofif of a Modified Neurotoxin Dendroaspin on Its Activity of Platelet Aggregation and Cell Adhesion

机译：修饰的神经毒素树绿蛋白的RGd三肽基序中精氨酸的单取代对其血小板聚集活性和细胞粘附的影响

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The Arg-Gly-Asp(RGD)tripeptide unit is a cell-cell and cell-extracellular matrix recognition sequence fo some integrins that is found within several extracesllular matrix glycoproteins and dendroaspin, a disintegrin-like venom proteein isolated from the snake venom of the Dendroaspis jamsonii, In the present study, the RGD motif in dendroaspin was substituted by Lys-Gly-Asp(KGD), His-Gly-Asp(HGD),. Gln-Gly-Asp(QGd) and Ala-Gly-Asp(AGD) denoted as KGD-den , HGD-den, QGD-den and AGD-den, respectively. Each of the mutants exhibited activity as inhibitor of ADP-induced platedlet aggregation with IC_50 values of 0.26, 2.5, 6, and 17 μM for KGD-den, HGD-den, QGD-den, and AGD-den, respectively, as compared with RGD-den(IC_50 = 0.18μM). Interestingly, HGD-den was approx. two-fold more potent and a more selective inhibitor than either the KGD-den or QGD-den counterpart at blocking A375-SM human melanoma cell adhesion to bibrinogen (β_3mediated). KGD-den, HGD-den, and QGD-den were preferentially antagonists of A375-SM human melanoma cell adhesion to fibrinogen rather than to bibronectin(α_5β_1-,β_3-mediated). Both HGD-den and KGD-den were equipotent as inhibitors of human erythroleukaemia(HEL) cell adhesion to fibrinogen(IC_50 = 0.15μM) and also preferential inhibitors of HEL) ecll adhesion to fibrinogen (β_3 and β_1-mediated)rather than to fibronectin. These findins show that the presence fo the arginine within the RGD motif of dendroaspin is not obligatory and substitution of this residue can modulated inhibitory potency and integrin binding selectivity.
机译：Arg-Gly-Asp（RGD）三肽单元是一些整联蛋白的细胞-细胞和细胞-细胞外基质识别序列，存在于几种胞外基质糖蛋白和dendroaspin中，dendroaspin是从蛇毒的蛇毒中分离出的一种类似整合素的毒蛋白Dendroaspis jamsonii，在本研究中，Dendroaspin中的RGD基序被Lys-Gly-Asp（KGD），His-Gly-Asp（HGD）取代。 Gln-Gly-Asp（QGd）和Ala-Gly-Asp（AGD）分别表示为KGD-den，HGD-den，QGD-den和AGD-den。每个突变体均表现出作为ADP诱导的血小板凝集抑制剂的活性，与之相比，KGD-den，HGD-den，QGD-den和AGD-den的IC_50值分别为0.26、2.5、6和17μM。 RGD-den（IC_50 =0.18μM）。有趣的是，HGD-den约为。在阻断A375-SM人黑素瘤细胞对血纤蛋白原的粘附（β_3介导）方面，其效价和选择性都比KGD-den或QGD-den高两倍。 KGD-den，HGD-den和QGD-den是A375-SM人黑素瘤细胞粘附于纤维蛋白原而不是粘附于纤连蛋白（α_5β_1-，β_3介导的）的优先拮抗剂。 HGD-den和KGD-den都可以作为人红白血病细胞（HEL）粘附到纤维蛋白原的抑制剂（IC_50 =0.15μM），也可以作为HEL的优先抑制剂，而不是粘附到纤维蛋白原（β_3和β_1介导）而不是纤连蛋白。这些发现表明，在树突蛋白的RGD基序中精氨酸的存在不是必须的，并且该残基的取代可以调节抑制能力和整联蛋白结合选择性。

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