New m-calpain substrate-based azapeptide inhibitors.

TitleNew m-calpain substrate-based azapeptide inhibitors.
Publication TypeJournal Article
Year of Publication2013
AuthorsBánóczi, Z., Tantos Á., Farkas A., Majer Z., Dókus L. E., Tompa P., and Hudecz F.
JournalJ Pept Sci
Volume19
Issue6
Pagination370-6
Date Published2013 Jun
Type of Articleidp
ISSN1099-1387
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.

DOI10.1002/psc.2511
Alternate JournalJ. Pept. Sci.
PubMed ID23613308