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New m‐calpain substrate‐based azapeptide inhibitors
Author(s) -
Bánóczi Zoltán,
Tantos Ágnes,
Farkas Attila,
Majer Zsuzsa,
Dókus Levente E.,
Tompa Péter,
Hudecz Ferenc
Publication year - 2013
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2511
Subject(s) - calpain , proteases , cysteine , residue (chemistry) , amino acid , chemistry , enzyme , stereochemistry , intracellular , amino acid residue , biochemistry , inhibitory postsynaptic potential , peptide sequence , biology , gene , neuroscience
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 P 1 position was replaced with azaglycine (NH 2 ‐NH‐COOH) and further changes were made as follows: the N ‐terminal or/and C ‐terminal were truncated, amino acids were also changed at P 3 , P 2 , P′ 1 , or P′ 2 positions. Our results indicate that the identity of amino acid moieties between P 4 and P′ 5 positions is essential for the inhibitory activity. Only changes at position P 3 (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. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.