Suppression of vascular endothelium hyperpermeability by cell-permeating peptide inhibitors of myosin light chain kinase

Novel peptides originating from the peptide inhibitor of myosin light chain kinase (MLCK), L-PIK (Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys), have been studied for their ability to attenuate the thrombin-induced hyperpermeability of an endothelial cell monolayer in culture. Peptides N^αMeArg¹]-Lys-Lys-Tyr-Lys-Tyr-Arg-(D)Arg⁸-Lys and H-Arg(NO₂)Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH₂ (designated PIK2 and PIK4, respectively) appeared to be the most effective inhibitors of endothelial cell monolayer hyperpermeability, and surpassed other known peptide inhibitors of MLCK derived from original L-PIK. Our results validate PIK2 and PIK4 as the leading molecules for the development of novel drugs intended to counteract pathological hyperpermeability of vascular endothelium.