Using peptidic inhibitors to systematically probe the S1′ site of caspase-3 and caspase-7

被引：21

作者：

Goode, DR ^{[1
]}

Sharma, AK ^{[1
]}

Hergenrother, PJ ^{[1
]}

机构：

[1] Univ Illinois, Roger Adams Lab, Urbana, IL 61801 USA

来源：

ORGANIC LETTERS | 2005年 / 7卷 / 16期

关键词：

D O I：

10.1021/ol051287d

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Fifteen ketone-containing peptides were designed, synthesized, and used to probe the effect of substitution at the P1' position on caspase-3 and -7 inhibition. Even with the large bias of Ac-Asp-Glu-Val-Asp at the P4-P1 positions, certain peptides with cyclic functionality in the P1' position show a dramatically reduced ability to inhibit these caspases. Additionally, trends toward isozyme selectivity were also uncovered for particular P1' substituents. The data indicate that substitution in the P1' position can drastically affect both caspase inhibition and selectivity.

引用

页码：3529 / 3532

页数：4

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