The perfect penicillin?: Inhibition of a bacterial DD-peptidase by peptidoglycan-mimetic β-lactams

被引：30

作者：

Josephine, HR ^{[1
]}

Kumar, I ^{[1
]}

Pratt, RF ^{[1
]}

机构：

[1] Wesleyan Univ, Dept Chem, Middletown, CT 06459 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2004年 / 126卷 / 26期

关键词：

D O I：

10.1021/ja048850s

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

6-(Glycyl-L-α-aminopimelyl)-aminopenicillanic acid and 7-(glycyl-L-α-aminopimelyl)-aminocephalosporanic acid have been synthesized as Streptomyces sp. peptidoglycan-mimetic β-lactams. These compounds inactivate the Streptomyces R61 DD-peptidase with rate constants of 1.5 × 107 s-1 M-1 and 5.6 × 105 s-1 M-1, respectively. The former compound is thus the most effective β-lactam inhibitor of a DD-peptidase yet described. The analogous D-alanyl-D-alanine peptide has previously been shown to react with this enzyme with comparable efficiency, kcat/Km = 8.7 × 106 s-1 M-1. These results show that, in this case at least, incorporation of a peptidoglycan-mimetic side chain into a β-lactam greatly enhances its activity as a DD-peptidase inhibitor. This result has interesting implications for β-lactam design. Copyright © 2004 American Chemical Society.

引用

页码：8122 / 8123

页数：2

共 17 条

[1] On the substrate specificity of bacterial DD-peptidases: evidence from two series of peptidoglycan-mimetic peptides [J].