Rational design of azepane-glycoside antibiotics targeting the bacterial ribosome

被引：42

作者：

Barluenga, S

Simonsen, KB

Littlefield, ES

Ayida, BK

Vourloumis, D

Winters, GC

Takahashi, M

Shandrick, S

Zhao, Q

Han, Q

Hermann, T

机构：

[1] Anadys Pharmaceut Inc, Dept RNA Biochem, San Diego, CA 92121 USA

[2] Anadys Pharmaceut Inc, Dept Med Chem, San Diego, CA 92121 USA

[3] Anadys Pharmaceut Inc, Dept Struct Chem, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 03期

关键词：

antibiotics; RNA; structure-based design;

D O I：

10.1016/j.bmcl.2003.11.028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

RNA recognition by natural aminoglycoside antibiotics depends on the 2-deoxystreptamine (2-DOS) scaffold which participates in specific hydrogen bonds with the ribosomal decoding-site target. Three-dimensional structure information has been used for the design of azepane-monoglycosides, building blocks for novel antibiotics in which 2-DOS is replaced by a heterocyclic scaffold. Azepane-glycosides showed target binding and translation inhibition in the low micromolar range and inhibited growth of Staphylococcus aureus, including aminoglycoside-resistant strains. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：713 / 718

页数：6

共 44 条

[1] Probing the specificity of aminoglycoside ribosomal RNA interactions with designed synthetic analogs [J].