Design, synthesis of novel tryptophan derivatives for antiplatelet aggregation activity based on tripeptide pENW (pGlu-Asn-Trp)
Design, synthesis of novel tryptophan derivatives for antiplatelet aggregation activity based on tripeptide pENW (pGlu-Asn-Trp)
复制标题
基于三肽pENW（pGlu-Asn-Trp）设计、合成具有抗血小板聚集活性的新型色氨酸衍生物
DOI：
10.1016/j.ejmech.2015.07.016
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发表时间：
2015-09-18
影响因子：
6.7
通讯作者：
Li, Zhiyu
中科院分区：
文献类型：
--
作者：
Xie, Zhouling;Feng, Sen;Li, Zhiyu
pENW是一种来源于尖吻蝮蛇（AgkistrodonacutusGuenther）毒液的三聚体肽，已发现它是GPIIb/IIIa受体的拮抗剂，并显示出抗血小板聚集活性。以pENW和GPIIb/IIIa抑制剂替罗非班为基础，设计、合成了一系列色氨酸衍生物，并对其抗ADP诱导的血小板聚集活性进行了评价。还测试了最有效的化合物87与替罗非班相比的出血时间和体内抗血栓形成活性。结果表明，87的抗血小板聚集活性与替罗非班相似，但出血风险低于替罗非班，是一个值得进一步研究的先导化合物。(C)2015年Elsevier Masson SAS。All rights reserved.
pENW, a three mer peptide derived from Agkistrodon acutus Guenther venom, has been found to be an antagonist of the GPIlb/IIIa receptor and shows antiplatelet aggregation activity. Based on pENW and a GPIIb/IIIa inhibitor Tirofiban, a series of tryptophan derivatives were designed, synthesized and evaluated for their antiplatelet aggregation activity induced by ADP. The most potent compound 87 was also tested for the bleeding time and antithrombotic activity in vivo in comparison with Tirofiban. The results indicated that 87 shows similar antiplatelet aggregation activity as Tirofiban to the aggregation of platelet induced by all of the four agonists, but has lower bleeding risk than Tirofiban, representing a promising lead compound for further study. (C) 2015 Elsevier Masson SAS. All rights reserved.