Synthesis and Biological Activity ofN-Sulfonyltripeptides with C-Terminal Arginine as Potential Serine Proteases Inhibitors.
Tripeptides of the general X-SO2-d-Ser-AA-Arg-CO-Y formula, where X =α-tolyl,p-tolyl, 2,4,6-triisopropylphenyl; AA = alanine, glycine, norvaline and Y = OH, NH-(CH2)5NH2were obtained and tested for their effect on the amidolytic activities of urokinase, thrombin, trypsin, plasmin, t-PA and kallikrein. The most active compound towards urokinase was PhCH2SO2-d-Ser-Gly-Arg-OH with Kivalue 5.4 μM and the most active compound toward thrombin was PhCH2SO2-d-Ser-NVa-Arg-OH with Kivalue 0.82 μM. The peptides were nontoxic against porcine erythrocytes in vitro. PhCH2SO2-d-Ser-Gly-Arg-OH showed cytotoxic effect against DLD cell lines with IC50values of 5 μM. For the highly selective determination of the interaction of some of the synthesised acids of tripeptides with urokinase and plasmin the Surface Plasmon Resonance Imaging sensor has been applied. These compounds bind to urokinase and plasmin in 0.05 mM concentration.
Department of Organic Chemistry, Medical University of Bialystok, Kilinski 1 Str., 15-089 Białystok, Poland.
Agnieszka
A
Markowska
Magdalena
M
Bruzgo
Ewa
E
Gorodkiewicz
Arkadiusz
A
Surażyński
Amidolytic activity; Cancer cells activity; Serine proteases inhibitor; Surface Plasmon Resonance Imaging; Urokinase inhibitor