title: New m-calpain substrate-based azapeptide inhibitors.
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.
authors.affiliation: Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Budapest, Hungary. banoczi@elte.hu
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Bánóczi
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Tantos
authors.forename: Attila
authors.initials: A
authors.lastname: Farkas
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Majer
authors.forename: Levente E
authors.initials: LE
authors.lastname: Dókus
authors.forename: Péter
authors.initials: P
authors.lastname: Tompa
authors.forename: Ferenc
authors.initials: F
authors.lastname: Hudecz
mesh_terms: D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D001372:Aza Compounds; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D002154:Calpain; C449000:m-calpain