Abstract
Anthrax lethal factor is a Zn(2+)-dependent metalloprotease and the key virulence factor of tripartite anthrax toxin secreted by Bacillus anthracis, the causative agent of anthrax. A series of guanidinylated 2,5-dideoxystreptamine derivatives were designed and synthesized as inhibitors of lethal factor, some of which show strong inhibitory activity against lethal factor in an in vitro FRET assay. Preparation and structure-activity relationships of these compounds are presented.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Bacillus anthracis / enzymology*
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Bacterial Toxins / antagonists & inhibitors*
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Guanidine / chemistry*
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Hexosamines / chemical synthesis
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Hexosamines / chemistry
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Hexosamines / pharmacology
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Metalloendopeptidases / antagonists & inhibitors*
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Models, Molecular
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Molecular Structure
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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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Structure-Activity Relationship
Substances
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Bacterial Toxins
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Hexosamines
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Protease Inhibitors
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streptamine
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Metalloendopeptidases
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Guanidine