title: [Peptide inhibitors of myosin light chain kinase. Development of peptidase resistant analogues].
abstract: Myosin light chain kinase (MLCK) is the key regulator of various forms of cell motility including endothelial and epithelial permeability in particular. One of the potential MLCK inhibitors to be used in humans is a membrane permeable peptide H-RKKYKYRRK-NH2 (L-PIK). In present work we used solid phase peptide synthesis and Fmoc-technology to produce five modifications of L-PIK. Based on (1)H NMR analysis revealed that these peptides demonstrated improved resistance to degradation in blood plasma. One of de novo synthesized peptides, L-[MeArg(1)]PIK inhibited MLCK activity in vitro with the same efficiency as L-PIK whereas other modified peptides showed reduced inhibitory activity. D-amino acid analog of PIK was the least active inhibitor. Thus, we have demonstrated the possibility to produce an effective MLCK peptide inhibitor with increased resistance to biodegradation that is suitable for further pharmacological development.
authors.forename: A V
authors.initials: AV
authors.lastname: Sekridova
authors.forename: M V
authors.initials: MV
authors.lastname: Sidorova
authors.forename: A A
authors.initials: AA
authors.lastname: Az'muko
authors.forename: A S
authors.initials: AS
authors.lastname: Molokoedov
authors.forename: V N
authors.initials: VN
authors.lastname: Bushuev
authors.forename: A V
authors.initials: AV
authors.lastname: Marchenko
authors.forename: O V
authors.initials: OV
authors.lastname: Shcherbakova
authors.forename: V P
authors.initials: VP
authors.lastname: Shirinskiĭ
authors.forename: Zh D
authors.initials: ZhD
authors.lastname: Bespalova
mesh_terms: D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D010447:Peptide Hydrolases / Q000737:chemistry*; D010949:Plasma / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D009219:Myosin-Light-Chain Kinase; D010447:Peptide Hydrolases