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Selective inhibition of bacterial and human topoisomerases by N-arylacyl O-sulfonated aminoglycoside derivatives.

ABSTRACT: 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 non-specific 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 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.

SUBMITTER: Fenner AM

PROVIDER: S-EPMC3694624 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Selective inhibition of bacterial and human topoisomerases by N-arylacyl O-sulfonated aminoglycoside derivatives.

Fenner Amanda M AM Oppegard Lisa M LM Hiasa Hiroshi H Kerns Robert J RJ

ACS medicinal chemistry letters 20130501 5

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 non-specific interactions with many proteins. In this study N-arylacyl O-sulfonated aminoglycosides were synthesized and evaluated for their ability to selectively inhibit ...[more]

PMID: 23814643

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