Synthesis and biological activity of N-sulfonyltripeptides with C-terminal arginine as potential serine proteases inhibitors

Abstract

Tripeptides of the general X-SO 2 -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-(CH 2 ) 5 NH 2 were 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 PhCH 2 SO 2 -d-Ser-Gly-Arg-OH with K i value 5.4 μM and the most active compound toward thrombin was PhCH 2 SO 2 -d-Ser-NVa-Arg-OH with K i value 0.82 μM. The peptides were nontoxic against porcine erythrocytes in vitro. PhCH 2 SO 2 -d-Ser-Gly-Arg-OH showed cytotoxic effect against DLD cell lines with IC 50 values 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. © 2012 The Author(s).