Synthesis and structure-activity relationships of o-sulfonamidoarylhydrazides as inhibitors of LL-diaminopimelate aminotransferase (LL-DAP-AT)

被引：5

作者：

Fan, Chenguang ^{[1
]}

Vederas, John C. ^{[1
]}

机构：

[1] Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2012年 / 10卷 / 30期

基金：

加拿大自然科学与工程研究理事会;

关键词：

LYSINE BIOSYNTHESIS; PEPTIDOGLYCAN STRUCTURE; SUBSTRATE RECOGNITION; ENZYME; CATALYSIS; MECHANISM; INSIGHTS; PATHWAY; PLANTS; TARGET;

D O I：

10.1039/c2ob00040g

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Recently, LL-diaminopimelate aminotransferase (LL-DAP-AT), a pyridoxal-5'-phosphate (PLP)-dependent enzyme, was reported to catalyze a key step in the biosynthesis of L-lysine in plants and Chlamydia. Previous screening of a 29 201-compound library against LL-DAP-AT identified an o-sulfonamidoarylhydrazide as a reversible inhibitor with IC50 similar to 5 mu M. Structure-activity relationship (SAR) studies based on this lead compound identified key structural features essential for enzyme inhibition and led to slightly improved inhibitors. Preliminary studies on the mode of inhibition of LL-DAP-AT by this class of compounds are also reported.

引用

页码：5815 / 5819

页数：5

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