New m-calpain substrate-based azapeptide inhibitors

Bánóczi, Zoltán and Tantos, Ágnes and Farkas, Attila and Majer, Zsuzsa and Dókus, Endre Levente and Tompa, Péter and Hudecz, Ferenc (2013) New m-calpain substrate-based azapeptide inhibitors. JOURNAL OF PEPTIDE SCIENCE, 19 (6). pp. 370-376. ISSN 1075-2617

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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. © 2013 European Peptide Society and John Wiley & Sons, Ltd.

Item Type: Article
Uncontrolled Keywords: reversed phase high performance liquid chromatography; PROTEIN SECONDARY STRUCTURE; priority journal; PEPTIDE SYNTHESIS; enzyme inhibition; carboxy terminal sequence; ARTICLE; amino terminal sequence; unclassified drug; protein inhibitor; calpain 2; azapeptide inhibitor; enzyme inhibitor; CYSTEINE PROTEASES; CALPAIN; Azapeptide
Subjects: Q Science / természettudomány > QD Chemistry / kémia
Q Science / természettudomány > QD Chemistry / kémia > QD01 Analytical chemistry / analitikai kémia
Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia
Depositing User: MTMT SWORD
Date Deposited: 04 Nov 2013 15:12
Last Modified: 04 Nov 2013 15:12

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