Tripeptides with non-code amino acids as potential serine proteases inhibitors.
Eight peptides of the general H-D-Ser-AA-Arg-OH formula, where AA = phenylglycine, phenylalanine, homophenylalanine, cyclohexylglycine, cyclohexylalanine, homocyclohexylalanine, α-methylphenylalanine and 1-aminocyclohexyl carboxylic acid were obtained and tested for their effect on the amidolytic activities of urokinase, thrombin, trypsin, plasmin, t-PA and kallikrein. We tested the hemolytic activity of the peptides against porcine erythrocytes and the antitumor activity against the human breast cancer cells, standard MCF-7 and estrogen-independent MDA-MB-231. The most active compounds were H-D-Ser-Chg-Arg-OH towards thrombin and H-D-Ser-Phg-Arg-OH towards plasmin with K(i) value 5.02 μM and 5.7 μM, respectively.
Department of Organic Chemistry, Poland. agnieszka.markowska@umb.edu.pl
Agnieszka
A
Markowska
Magdalena
M
Bruzgo
Arkadiusz
A
Surażyński
Krystyna
K
Midura-Nowaczek
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D007610:Kallikreins; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator