Novel peptide inhibitors of myosin light chain kinase suppress the hyperpermeability of vascular endothelium

The ability of novel cell-permeating peptide molecules derived from the peptide inhibitor of myosin light chain kinase (MLCK), L-PIK (Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys) to inhibit this kinase in vitro and attenuate the thrombin-induced hyperpermeability of endothelial cell monolayer in culture has been studied. It was found that compounds N^αMeArg¹]-L-PIK and Cit¹]-L-PIK possess inhibitory activity towards MLCK comparable to that of L-PIK and the ability to suppress the hyperpermeability of endothelium, whereas other modifications of L-PIK were less effective. Thus, among de novo synthesized peptides, N^αMeArg¹]-L-PIK and Cit¹]-L-PIK demonstrate the inhibitory properties of the original peptide L-PIK and additionally surpass it in stability in blood plasma. These peptides may be used in the design of novel antiedemic drugs.