[Novel peptide inhibitors of the myosin light chain kinase suppress hyperpermeability of vascular endothelium].
The ability of novel cell-permeating peptide molecules derived from the peptide inhibitor of the 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 the compounds [NalphaMeArg1]-L-PIK and [Cit1]-L-PIK possess the 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, [NalphaMeArg1]-L-PIK and [Cit1]-L-PIK demonstrate the inhibitory properties of the original peptide L-PIK and additionally surpass it by stability in blood plasma. These peptides may be used in the design of novel antiedemic drugs.
A V
AV
Marchenko
E O
EO
Stepanova
A V
AV
Sekridova
M V
MV
Sidorova
V N
VN
Bushuev
Zh D
ZhD
Bespalova
V P
VP
Shirinskiĭ
D000818:Animals; D002417:Cattle; D002460:Cell Line; D002463:Cell Membrane Permeability; D002645:Chickens; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D009130:Muscle, Smooth / Q000201:enzymology; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D009842:Oligopeptides / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000494:pharmacology
C118153:Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2; D009842:Oligopeptides; D009219:Myosin-Light-Chain Kinase; D013917:Thrombin