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 K-i value of 2.09 muM. Surprisingly, inhibitor 1 having the D-configuration is more potent (K-i = 1.54 muM) than its antipode by about 3-fold. A possible expla nation for the stereochemistry observed in the inhibition of CPA with 1 is presented. (C) 2000 Elsevier Science Ltd. All rights reserved.