Tripeptides with non-code amino acids as potential serine proteases inhibitors

J Enzyme Inhib Med Chem. 2013 Jun;28(3):639-43. doi: 10.3109/14756366.2011.651463. Epub 2012 Feb 3.

Abstract

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Erythrocytes / drug effects
  • Female
  • Fibrinolysin / antagonists & inhibitors
  • Humans
  • Kallikreins / antagonists & inhibitors
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology*
  • Serine Proteinase Inhibitors / chemistry*
  • Serine Proteinase Inhibitors / pharmacology*
  • Swine
  • Thrombin / antagonists & inhibitors
  • Tissue Plasminogen Activator / antagonists & inhibitors
  • Trypsin Inhibitors / chemistry
  • Trypsin Inhibitors / pharmacology
  • Urokinase-Type Plasminogen Activator / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Oligopeptides
  • Serine Proteinase Inhibitors
  • Trypsin Inhibitors
  • Kallikreins
  • Thrombin
  • Tissue Plasminogen Activator
  • Fibrinolysin
  • Urokinase-Type Plasminogen Activator