New m-calpain substrate-based azapeptide inhibitors

Zoltán Bánóczi, Ágnes Tantos, Attila Farkas, Zsuzsa Majer, Levente E. Dókus, Péter Tompa, Ferenc Hudecz

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Calpains are intracellular cysteine proteases with several important physiological functions. Calpain inhibitors may be promising tools in the analysis of the function of the enzyme in diseases caused by overexpression/activation. Here, we report on the synthesis, solution conformation, and characterization of novel group of azapeptides whose sequences originate from an efficient m-calpain substrate, TPLKSPPPSPR, described by us earlier and possess varying levels of calpain inhibition. The Lys residue at P1 position was replaced with azaglycine (NH2-NH-COOH) and further changes were made as follows: the N-terminal or/and C-terminal were truncated, amino acids were also changed at P3, P2, P′1, or P′2 positions. Our results indicate that the identity of amino acid moieties between P4 and P′5 positions is essential for the inhibitory activity. Only changes at position P3 (Pro) are tolerated. Azapeptide analogs, described in this communication could be considered as useful set of compounds for elucidation of the enzyme interaction at P and P′ sites.

Original languageEnglish
Pages (from-to)370-376
Number of pages7
JournalJournal of Peptide Science
Volume19
Issue number6
DOIs
Publication statusPublished - Jun 1 2013

Keywords

  • Azapeptide
  • Calpain
  • Cysteine proteases
  • Enzyme inhibitor

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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