Selective Inhibition of Bacterial and Human Topoisomerases by N-Arylacyl O-Sulfonated Aminoglycoside Derivatives
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- 作者：Amanda M. Fenner ; Lisa M. Oppegard ; Hiroshi Hiasa ; Robert J. Kerns
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：May 9, 2013
- 年：2013
- 卷：4
- 期：5
- 页码：470-474
- 全文大小：286K
- 年卷期：v.4,no.5(May 9, 2013)
- ISSN：1948-5875
文摘
Numerous therapeutic applications have been proposed for molecules that bind heparin-binding proteins. Development of such compounds has primarily focused on optimizing the degree and orientation of anionic groups on a scaffold, but utility of these polyanions has been diminished by their typically large size and nonspecific interactions with many proteins. In this study, N-arylacyl O-sulfonated aminoglycosides were synthesized and evaluated for their ability to selectively inhibit structurally similar bacterial and human topoisomerases. It is demonstrated that the structure of the aminoglycoside and of the N-arylacyl moiety imparts selective inhibition of different topoisomerases and alters the mechanism. The results here outline a strategy that will be applicable to identifying small, structurally defined oligosaccharides that bind heparin-binding proteins with a high degree of selectivity.