Penetrating peptide inhibitor of the myosin light chain kinase suppresses hyperpermeability of vascular endothelium

A. V. Marchenko*, M. V. Sidorova, A. V. Sekridova, V. N. Bushuev, V. L. Lakomkin, T. R. Orlova, O. V. Stepanova, V. I. Kapel'ko, D. M. Watterson, L. J. Van Eldik, Z. D. Bespalova, V. P. Shirinskiǐ

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Nonapeptide H-Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2 corresponding to a modified sequence of autoinhibitory region of myosin light chain kinase (MLCK) was synthesized from L-amino acids and from D-amino acids. Using nuclear magnetic resonance spectroscopy it has been demonstrated that D-peptide is significantly more stable in human blood plasma than its L-enantiomer. D-peptide accumulated in cultured human umbilical vein endothelial cells suppressed development of hyperpermeability in endothelial monolayer induced by thrombin addition. Following intravenous administration D-peptide decreased the extent of lung oedema in rats induced by infusion of oleic acid in bloodstream. Thus, the peptide molecules based on an autoinhibitory peptide of MLCK may serve as a prototype for development of a novel antioedematous drugs that directly affect the MLCK-dependent motile processes in vascular endothelium.

Original languageEnglish (US)
Pages (from-to)507-515
Number of pages9
JournalRossiǐskii fiziologicheskiǐ zhurnal imeni I.M. Sechenova / Rossiǐskaia akademiia nauk
Volume95
Issue number5
StatePublished - May 1 2009

ASJC Scopus subject areas

  • Medicine(all)

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