Design, synthesis and evaluation of D-homophenylalanyl epoxysuccinate inhibitors of the trypanosomal cysteine protease cruzain

被引：27

作者：

Roush, WR ^{[1
]}

Hernandez, AA

McKerrow, JH

Selzer, PM

Hansell, E

Engel, JC

机构：

[1] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA

[2] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94121 USA

来源：

TETRAHEDRON | 2000年 / 56卷 / 50期

关键词：

enzyme inhibitors; hydroxamic acids and derivatives; molecular design; peptide analogs and mimetics;

D O I：

10.1016/S0040-4020(00)00882-6

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The binding modes of E-64c to papain combined with molecular modeling and ligand design using the crystal structure of cruzain have been used to develop new, potent D-Homophenylalanyl epoxysuccinate inhibitors of cruzain, the major cysteine protease of Trypanosoma cruzi. The most potent inhibitor 47 contains an O-benzyl hydroxamate unit and is highly specific for cruzain relative to other cysteine proteases tested. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：9747 / 9762

页数：16

共 73 条

[71] IRREVERSIBLE INHIBITION OF PAPAIN BY EPOXYSUCCINYL PEPTIDES - C-13 NMR CHARACTERIZATION OF THE SITE OF ALKYLATION [J].