N-(Hydroxyaminocarbonyl)phenylalanine: a novel class of inhibitor for carboxypeptidase A.
N-(Hydroxyaminocarbonyl)phenylalanine (1) was designed rationally as a new type of inhibitor for carboxypeptidase A (CPA). The designed inhibitor was readily prepared from phenylalnine benzyl ester in two steps and evaluated to find that rac-1 inhibits CPA in a competitive fashion with the Ki value of 2.09 microM. Surprisingly, inhibitor 1 having the D-configuration is more potent (Ki = 1.54 microM) than its antipode by about 3-fold. A possible explanation for the stereochemistry observed in the inhibition of CPA with 1 is presented.
Chung
S J
SJ
Center for Biofunctional Molecules and Departnent of Chemistry, Pohang University of Science and Technology, Namgu, South Korea.
Kim
D H
DH
D001665:Binding Sites; D001667:Binding, Competitive; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D043422:Carboxypeptidases A; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D007700:Kinetics; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
D004791:Enzyme Inhibitors; C425765:N-(hydroxyaminocarbonyl)phenylalanine; D010649:Phenylalanine; D014508:Urea; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D006918:Hydroxyurea