Journal
TOXICON
Volume 54, Issue 5, Pages 575-582Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2009.03.016
Keywords
Botulism; Botulinum neurotoxin A; Botulinum neurotoxin B; Light chain metalloprotease; Protease inhibitors
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Funding
- NIAID NIH HHS [AI30050, N01 AI030050] Funding Source: Medline
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Botulinum neurotoxins (BoNTs), proteins secreted by the bacteria genus Clostridium, represent a group of extremely lethal toxins and a potential bioterrorism threat. As the current therapeutic options are of a predominantly prophylactic nature and cannot be used en masse, new strategies and ultimately potential treatments are desperately needed to combat any widespread release of these neurotoxins. In these regards, our laboratory has been working on developing new alternatives to treat botulinum intoxication through the development of inhibitors of the light chain proteases, the etiological agent which causes BoNT intoxication. Such a strategy has required the construction of two high-throughput screens and small molecule non-peptidic libraries; excitingly, inhibitors of the BoNT/A protease have been uncovered and are being optimized via structure activity relationship studies. Published by Elsevier Ltd.
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