A new type of carboxypeptidase A inhibitor: Design, synthesis, and mechanistic implication

Dong H. Kim, Young Mi Kim, Zhi Hong Li, Kyung Bo Kim, So Yeon Choi, Sangsoo Kim

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

2-Benzyl-3,4-epoxybutanoic acid (BEBA) which was designed rationally as an irreversible inhibitor of carboxypeptidase A on the basis of the known topology of the active site and catalytic mechanism of the enzyme indeed inactivated the enzyme very efficiently with a covalent modification at the carboxylate of Glu-270. The partition ratio of BEBA was determined to be 20.3. Of four stereoisomers of BEBA, (2S, 3R)-and (2R, 3S)-BEBA show the inhibitory activity, and the other two isomers are essentially inactive. This stereospecificity of BEBA in the inhibition was explained with a proposition of a three-dimensional representation of the active site of the enzyme. All four stereoisomers were synthesized effectively and conveniently starting with optically active 2-benzyl-2-vinylacetic acid which was obtained by a kinetic resolution of racemic methyl ester of the acid using a-chymotrypsin.

Original languageEnglish
Pages (from-to)721-728
Number of pages8
JournalPure and Applied Chemistry
Volume66
Issue number4
DOIs
StatePublished - 1994

Bibliographical note

Funding Information:
Authors express their sincere thanks to the Korea Science and Engineering Foundation for the support of this work.

ASJC Scopus subject areas

  • Chemistry (all)
  • Chemical Engineering (all)

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