Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors

被引：15

作者：

Shirazi, Amir Nasrolahi ^{[1
]}

Tiwari, Rakesh Kumar ^{[1
]}

Brown, Alex ^{[2
]}

Mandal, Dindyal ^{[1
]}

Sun, Gongqin ^{[2
]}

Parang, Keykavous ^{[1
]}

机构：

[1] Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA

[2] Univ Rhode Isl, Dept Cell & Mol Biol, Kingston, RI 02881 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 11期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

Arginine; Cyclic peptides; Src; Tryptophan; Tyrosine kinase; SH2; DOMAIN; TYROSINE; IDENTIFICATION; DESIGN; ANALOGS;

D O I：

10.1016/j.bmcl.2013.03.124

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A number of cyclic and linear peptides containing various combinations of amino acids were evaluated for their Src kinase inhibitory potency. Among all the peptides, cyclic decapeptide C[RW](5) containing alternative arginine (R) and tryptophan (W) residues was found to be the most potent Src kinase inhibitor. C[RW](5) showed higher inhibitory activity (IC50 = 2.8 mu M) than C[KW](5), L(KW)(5), C[RW](4), and C[RW](3) with IC50 values of 46.9, 69.1, 21.5, and 25.0 mu M, respectively, as determined in a fluorescence intensity-based assay. Thus, the cyclic nature, the presence of arginine, ring size, and the number of amino acids in the structure of the peptide were found to be critical in Src kinase inhibitory potency. The IC50 value of C[RW](5) was found to be 0.8 mu M in a radioactive assay using [gamma-P-32]-ATP and polyE(4)Y as the substrate. C[RW](5) was a noncompetitive Src kinase inhibitor, showing approximately fourfold more selectivity towards Src than Abl. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：3230 / 3234

页数：5

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