Tripeptides with C-terminal arginine as potential inhibitors of urokinase

Article abstract of DOI:10.1007/s10989-011-9239-y

We synthesized and tested ten peptides with the molecular structure being H-d-Ser-AA-Arg-OH for their effect on the amidolytic activities against urokinase, thrombin, trypsin, plasmin, tissue plasminogen activator and kallikrein. The inserted amino acid in each peptide was either leucine, norleucine, izoleucine, valine, norvaline, α-metyloalanine, α-aminobutanoic acid, homoleucine, tert-leucine or neoglycine. H-d-Ser-NVal-Arg-OH (compound 4) was the most active inhibitor of urokinase plasminogen activator with a K_i value of 0.85 μM. Compound 4 showed cytotoxic effect against MDA-MB-231 and DLD cell lines, respectively, with IC₅₀ values of 25 and 19 μM. Synthesised compounds did not have activity against MCF-7 cancer cells. These peptides were nontoxic against pig's erythrocytes in vitro.