Discovery of highly potent Src SH2 binders:: Structure-activity studies and X-ray structures

被引：9

作者：

Deprez, P ^{[1
]}

Baholet, I ^{[1
]}

Burlet, S ^{[1
]}

Lange, G ^{[1
]}

Amengual, R ^{[1
]}

Schoot, B ^{[1
]}

Vermond, A ^{[1
]}

Mandine, E ^{[1
]}

Lesuisse, D ^{[1
]}

机构：

[1] Aventis Pharma, Paris Res Ctr, Med Chem, F-93235 Romainville, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 09期

关键词：

D O I：

10.1016/S0960-894X(02)00139-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Optimization of the hydrophobic moiety of caprolactam/thiazepinone based compounds led to the identification of potent Src SH2 binders in two different series incorporating a phosphotyrosine group (RU 81843) or a phosphobenzoic group (RU 79181). The X-ray co-structures with the Src SH2 domain revealed different binding modes for RU 81843 and RU 79181, and an excellent fit between RU81843 and the Src SH2 protein thus explaining its high potency (9 nM, 15-fold more potent than pYEE1 reference peptide). (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1291 / 1294

页数：4

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