Inhibition of aminopeptidases by N-aminoacyl-O-4-nitrobenzoyl hydroxamates.
10 N-aminoacyl-O-4-nitrobenzoyl hydroxamates were investigated as potential inhibitors of aminopeptidases. While the metal-depending enzymes aminopeptidase M, aminopeptidase P and leucine aminopeptidase were inhibited reversibly by the compounds, the thiol enzyme cathepsin H was inhibited efficiently in time-dependent reactions according to its substrate specificity. N-phenylalanyl-O-4-nitrobenzoyl hydroxamate was shown to be most effective, exhibiting a second-order-rate constant of inhibition of 31,766 M-1 s-1.
Department of Biochemistry and Biotechnology, Martin-Luther-University, Halle, Germany.
H U
HU
Demuth
A
A
Stöckel
A
A
Schierhorn
S
S
Fittkau
H
H
Kirschke
D
D
Brömme
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D056655:Cathepsin H; D002403:Cathepsins / Q000037:antagonists & inhibitors; D003546:Cysteine Endopeptidases; D006863:Hydrogen-Ion Concentration; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013379:Substrate Specificity
D006877:Hydroxamic Acids; C083583:4-nitrobenzoyl N-phenylalanylhydroxamate; D010649:Phenylalanine; D002403:Cathepsins; D000626:Aminopeptidases; D003546:Cysteine Endopeptidases; D056655:Cathepsin H