Peptidyl hydroxamic acids as methionine aminopeptidase inhibitors.
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.
Hu
Xubo
X
Department of Chemistry and Ohio State Biochemistry Program, The Ohio State University, 100 West 18th Avenue, Columbus, OH 43210, USA.
Zhu
Jinge
J
Srivathsan
Sumant
S
Pei
Dehua
D
D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology; D063208:Methionyl Aminopeptidases; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*
D029968:Escherichia coli Proteins; D006877:Hydroxamic Acids; D011480:Protease Inhibitors; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases