New m-calpain substrate-based azapeptide inhibitors
Article first published online: 24 APR 2013
Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 19, Issue 6, pages 370–376, June 2013
How to Cite
Bánóczi, Z., Tantos, Á., Farkas, A., Majer, Z., Dókus, L. E., Tompa, P. and Hudecz, F. (2013), New m-calpain substrate-based azapeptide inhibitors. J. Peptide Sci., 19: 370–376. doi: 10.1002/psc.2511
- Issue published online: 10 MAY 2013
- Article first published online: 24 APR 2013
- Manuscript Revised: 5 MAR 2013
- Manuscript Accepted: 5 MAR 2013
- Manuscript Received: 18 JAN 2013
- cysteine proteases;
- enzyme inhibitor
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. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.