Abstract |
Botulinum neurotoxins, responsible for the neuroparalytic syndrome botulism, are the deadliest of known biological toxins. The work described in this study was based on a three-zone pharmacophore model for botulinum neurotoxin serotype A light chain inhibition. Specifically, the pharmacophore defined a separation between the overlaps of several different, non- zinc(II)-coordinating small molecule chemotypes, enabling the design and synthesis of a new structural hybrid possessing a Ki=600 nM (+/-100 nM).
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Authors | J C Burnett, C Wang, J E Nuss, T L Nguyen, A R Hermone, J J Schmidt, R Gussio, P Wipf, S Bavari |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 19
Issue 19
Pg. 5811-3
(Oct 01 2009)
ISSN: 1464-3405 [Electronic] England |
PMID | 19703771
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Neurotoxins
- Protease Inhibitors
- Botulinum Toxins, Type A
- Zinc
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Topics |
- Botulinum Toxins, Type A
(antagonists & inhibitors, metabolism)
- Drug Design
- Neurotoxins
(antagonists & inhibitors, metabolism)
- Protease Inhibitors
(chemical synthesis, chemistry, pharmacology)
- Stereoisomerism
- Structure-Activity Relationship
- Zinc
(chemistry)
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