Journal article
Selective Inhibition of Bacterial and Human Topoisomerases by N-Arylacyl O-Sulfonated Aminoglycoside Derivatives
ACS medicinal chemistry letters, Vol.4(5), pp.470-474
03/25/2013
DOI: 10.1021/ml3004507
PMCID: PMC3694624
PMID: 23814643
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 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.
Details
- Title: Subtitle
- Selective Inhibition of Bacterial and Human Topoisomerases by N-Arylacyl O-Sulfonated Aminoglycoside Derivatives
- Creators
- Amanda M. Fenner - University of IowaLisa M. Oppegard - University of MinnesotaHiroshi Hiasa - University of MinnesotaRobert J. Kerns - University of Iowa
- Resource Type
- Journal article
- Publication Details
- ACS medicinal chemistry letters, Vol.4(5), pp.470-474
- Publisher
- American Chemical Society
- DOI
- 10.1021/ml3004507
- PMID
- 23814643
- PMCID
- PMC3694624
- ISSN
- 1948-5875
- eISSN
- 1948-5875
- Language
- English
- Date published
- 03/25/2013
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984365886802771
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