Abstract
A new class of methionine aminopeptidase (MetAP) inhibitors, which contain an internal hydroxamate (N-acyl-N-alkylhydroxylamine) core as the metal-chelating group, has been designed, synthesized, and tested. The compounds exhibited reversible, competitive inhibition against Escherichia coli MetAP as well as human MetAP-1 and MetAP-2. The most potent inhibitor had a K(i) value of 2.5 microM and >20-fold selectivity toward E. coli MAP.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aminopeptidases / antagonists & inhibitors*
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Aminopeptidases / metabolism
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Escherichia coli Proteins / antagonists & inhibitors
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Escherichia coli Proteins / metabolism
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Humans
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Hydroxamic Acids / chemistry*
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Hydroxamic Acids / pharmacology
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Methionyl Aminopeptidases
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
Substances
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Escherichia coli Proteins
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Hydroxamic Acids
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Protease Inhibitors
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Aminopeptidases
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Methionyl Aminopeptidases