Dissociation of antibacterial and hemolytic activities of an amphipathic peptide antibiotic

被引：39

作者：

Qin, CG

Zhong, XF

Bu, XZ

Ng, NLJ

Guo, ZH

机构：

[1] Hong Kong Univ Sci & Technol, Dept Chem, Kowloon, Hong Kong, Peoples R China

[2] Hong Kong Univ Sci & Technol, Biotechnol Res Inst, Kowloon, Hong Kong, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 23期

关键词：

D O I：

10.1021/jm0341352

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using an alanine-scanning method, we have found that the antibacterial and hemolytic activities of the amphipathic cyclic decapeptide antibiotic tyrocidine A depend on different structural components. Single substitution of glutamine-6 of the natural product with a cationic amino acid results in a therapeutic index enhancement of up to 140-fold. Successful dissociation of the two intimately associated properties should enable discovery of novel analogues with both high bacterial selectivity and antibacterial potency to counter microbial resistance.

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页码：4830 / 4833

页数：4

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