2-(4-AMINO-4-CARBOXYBUTYL)AZIRIDINE-2-CARBOXYLIC ACID - A POTENT IRREVERSIBLE INHIBITOR OF DIAMINOPIMELIC ACID EPIMERASE - SPONTANEOUS FORMATION FROM ALPHA-(HALOMETHYL)DIAMINOPIMELIC ACIDS

被引：61

作者：

GERHART, F ^{[1
]}

HIGGINS, W ^{[1
]}

TARDIF, C ^{[1
]}

DUCEP, JB ^{[1
]}

机构：

[1] MERRELL DOW RES INST,STRASBOURG CTR,16 RUE DANKARA,F-67084 STRASBOURG,FRANCE

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 08期

关键词：

D O I：

10.1021/jm00170a018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

2-(4-Amino-4-carboxybutyl)aziridine-2-carboxylic acid (3) (aziridino-DAP) was identified as the product of spontaneous hydrolysis of α-(halomethyl)diaminopimelic acids (a-halomethyl-DAPs) 2a-c. Under physiological conditions, 3 is an extremely potent irreversible inhibitor of the bacterial enzyme diaminopimelic acid epimerase (DAP-epimerase; EC 5.1.1.7). This unusual mode of action of an a-halomethyl amino acid with a non-pyridoxal enzyme is investigated. Synthesis and characterization of 2a-c and 3, kinetics of spontaneous formation of 3 from α-halomethyl-DAPs, and kinetics of enzyme inhibition by both 3 and by a-halomethyl-DAPs are reported. © 1990, American Chemical Society. All rights reserved.

引用

页码：2157 / 2162

页数：6

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