Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as src tyrosine kinase inhibitors
Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as src tyrosine kinase inhibitors
复制标题
DOI：
10.1021/jm060334k
复制
发表时间：
2006-06-01
影响因子：
7.3
通讯作者：
Parang, Keykavous
中科院分区：
文献类型：
--
作者：
Kumar, Anil;Ye, Guofeng;Parang, Keykavous
通过对Ac-CIYKYY（1）的侧链进行官能团修饰或引入构象限制，合成了一系列Ac-CIYKYY（1）的肽类似物，以提高其对活性Src激酶的抑制效力。Ac-CIYKF（4-NO2）Y（2，IC 50）0.53 μ M）和构象限制肽31（IC 50）0.28 μ M）分别显示出比1（IC 50）400 μ M）高750倍和1400倍的抑制活性。化合物2对ATP表现出部分竞争性抑制模式。
A series of peptide analogues of Ac-CIYKYY (1) were synthesized by functional group modifications in peptide side chains or by introducing conformational constraints, to improve the inhibitory potency against active Src kinase. Ac-CIYKF(4-NO2) Y ( 2, IC50) 0.53 mu M) and conformationally constrained peptide 31 (IC50) 0.28 mu M) exhibited 750- and 1400-fold higher inhibitory activities, respectively, versus that of 1 (IC50) 400 mu M). Compound 2 exhibited a partial competitive inhibition pattern against ATP.