Synthesis and calpain inhibitory activity of peptidomimetic compounds with constrained amino acids at the P2 position

Isaac Donkor, Rajani Korukonda

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The effect of incorporating α,α′-diethylglycine and α-aminocyclopentane carboxylic acid at the P2 position of inhibitors on μ-calpain inhibition was studied. Compound 3 with α,α′-diethylglycine was over 20-fold more potent than 2 with α-aminocyclopentane carboxylic acid. Additionally, 3 was over 35-fold selective for μ-calpain compared to cathepsin B, while 2 was 3-fold selective for cathepsin B compared to μ-calpain. Thus, the conformation induced by the P2 residue influenced the activities of the compounds versus the closely related cysteine proteases, and suggests an approach to the discovery of selective μ-calpain inhibitors.

Original languageEnglish (US)
Pages (from-to)4806-4808
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number17
DOIs
StatePublished - Sep 1 2008

Fingerprint

Peptidomimetics
Cathepsin B
Calpain
Carboxylic Acids
Amino Acids
Cysteine Proteases
Conformations
calpain inhibitors

All Science Journal Classification (ASJC) codes

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

Cite this

Synthesis and calpain inhibitory activity of peptidomimetic compounds with constrained amino acids at the P2 position. / Donkor, Isaac; Korukonda, Rajani.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 17, 01.09.2008, p. 4806-4808.

Research output: Contribution to journalArticle

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