title: Cysteine derivatives as inhibitors for carboxypeptidase A: synthesis and structure-activity relationships.
abstract: A series of cysteine (Cys) derivatives having an alkyl or arylalkyl moiety on the alpha-amino group of the amino acid have been synthesized as a novel type of inhibitor for carboxypeptidase A. These compounds are readily prepared starting with Cys in an optically active form. The structure-activity relationship study revealed that the inhibitors prepared from D-Cys are much more potent than the corresponding inhibitors obtained from L-Cys, and the most potent inhibitor in the series, (S)-1j with a K(i) value of 55 +/- 4 nM, is obtained by introducing a phenethyl moiety on the amino group of D-Cys. In comparison, the most active inhibitor in the series of 2-substituted 3-mercaptopropanoic acid is found to be 20, in which the phenyl ring is linked to the mercaptocarboxylic acid at the alpha-position with a methylene unit. A proposal that accounts for the different structural requirement for the maximum activity between the two series of inhibitors is provided.
authors.affiliation: Department of Chemistry, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyojadong, Namku, Pohang 790-784, Korea.
authors.forename: Jung Dae
authors.initials: JD
authors.lastname: Park
authors.forename: Dong H
authors.initials: DH
authors.lastname: Kim
mesh_terms: D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D043422:Carboxypeptidases A; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C448631:2-(mercaptomethyl)-3-phenylpropanoic acid; D004791:Enzyme Inhibitors; C448630:N-phenethylcysteine; D010666:Phenylpropionates; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D003545:Cysteine