Structural requirements for VanA activity of vancomycin analogues

被引：20

作者：

Chen, Z ^{[1
]}

Eggert, US ^{[1
]}

Dong, SD ^{[1
]}

Shaw, SJ ^{[1
]}

Sun, BY ^{[1
]}

LaTour, JV ^{[1
]}

Kahne, D ^{[1
]}

机构：

[1] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA

来源：

TETRAHEDRON | 2002年 / 58卷 / 32期

基金：

美国国家卫生研究院;

关键词：

vancomycin; glycopeptide analogues; vanA activity;

D O I：

10.1016/S0040-4020(02)00743-3

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

We have prepared several sets of glycopeptide analogues in order to probe the molecular basis for the activity of derivatives that overcome vanA resistance. The results described in this paper provide compelling evidence that good vanA activity is due to a mechanism of action that does not involve peptide binding. Hypothesizing that this mechanism of action involves an interaction of the disaccharide portion of vancomycin analogues with bacterial transglycosylases, we have prepared a compound in which the vancomycin aglycone is coupled to a known transglycosylase inhibitor that is structurally unrelated to the disaccharides that have been previously investigated. The activity of this compound is excellent. This work provides a clear prescription for the design of better glycopeptide analogues. (C) 2002 Published by Elsevier Science Ltd.

引用

页码：6585 / 6594

页数：10

共 18 条

[1] Molecular interactions of a semisynthetic glycopeptide antibiotic with D-alanyl-D-alanine and D-alanyl-D-lactate residues [J].