Abstract
Botulinum neurotoxin serotype A (BoNT/A) is the most toxic protein known to man and also a bioterrorism agent. As defined by our previous research targeting the etiological agent responsible for BoNT/A intoxication, a protease, we now report on the asymmetric synthesis of four new BoNT/A inhibitors; the most potent of this series is roughly 2-fold more active than the best small molecule inhibitor currently known.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Botulinum Toxins, Type A / antagonists & inhibitors*
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Botulinum Toxins, Type A / metabolism
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Botulinum Toxins, Type A / toxicity*
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Catalysis
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Clostridium / chemistry*
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Crystallography, X-Ray
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Humans
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology*
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Molecular Structure
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Neurotoxins / antagonists & inhibitors*
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Hydroxamic Acids
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Neurotoxins
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Protease Inhibitors
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Botulinum Toxins, Type A