Synthesis and calpain inhibitory activity of α-ketoamides with 2,3-methanoleucine stereoisomers at the P2 position

Isaac Donkor, Xiaozhang Zheng, Duane Miller

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

A series of novel ketoamides incorporating all four 2,3-methanoleucine stereoisomers at the P2 position was synthesized. The compounds displayed a wide variation in K(i) values for inhibition of calpain I depending on the configuration of the P2 methanoleucine residue. However, similar variation in cathepsin B inhibition was not observed suggesting that the S2 pocket of calpain I is more stereosensitive than that of cathepsin B. (C) 2000 Published by Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)2497-2500
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume10
Issue number22
DOIs
StatePublished - Nov 20 2000

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Cathepsin B
Stereoisomerism
Calpain
2,3-methanoleucine

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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AU - Zheng, Xiaozhang

AU - Miller, Duane

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AB - A series of novel ketoamides incorporating all four 2,3-methanoleucine stereoisomers at the P2 position was synthesized. The compounds displayed a wide variation in K(i) values for inhibition of calpain I depending on the configuration of the P2 methanoleucine residue. However, similar variation in cathepsin B inhibition was not observed suggesting that the S2 pocket of calpain I is more stereosensitive than that of cathepsin B. (C) 2000 Published by Elsevier Science Ltd.

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