Design of substrate-based inhibitors of human β-secretase

被引：107

作者：

Tung, JS ^{[1
]}

Davis, DL ^{[1
]}

Anderson, JP ^{[1
]}

Walker, DE ^{[1
]}

Mamo, S ^{[1
]}

Jewett, N ^{[1
]}

Hom, RK ^{[1
]}

Sinha, S ^{[1
]}

Thorsett, ED ^{[1
]}

John, V ^{[1
]}

机构：

[1] Elan Pharmaceut, San Francisco, CA 94080 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 02期

关键词：

D O I：

10.1021/jm0155695

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

By use of the effectively cleaved beta-secretase (BACE) substrate (1), incorporation of a statine in P-l resulted in a weak inhibitor 13 of the enzyme. Further substitution of P-1'-Asp by P-1'-Val in 13 results in a potent inhibitor 22 of BACE. Removal of the P-10-P-5 residues on the N-terminal part of inhibitor 22 resulted in no loss of potency (23). C-terminal truncations of inhibitor 22 generally led to significant loss of potency.

引用

页码：259 / 262

页数：4

共 14 条

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