Tetrapeptide substrates for the discrimination among kallikreins and other trypsin-like serine proteinases.
The three tetrapeptides Ac-Phe-Arg-Arg-Val-NH2 (I), Ac-Phe-Arg-Arg-Pro-NH2 (II) and Ac-Phe-Lys-Arg-Val-NH2 (III) were shown to form a most convenient substrate system for the discrimination of the serine proteinases listed below. Tissue kallikreins (porcine pancreatic, horse and human urinary) have the unique feature of cleaving well the Arg-Arg bond in peptide I (P'2 = Val), hardly splitting it in peptide II (P'2 = Pro). The kcat/Km for the hydrolysis of peptide II by horse urinary kallikrein was 600-fold lower than that for peptide I. Trypsin, plasma kallikreins (human and rat), tonin and rat urinary kallikrein were distinguished from each other by the sequence of the N-terminal fragments formed in the hydrolysis of peptides I and/or II. Differences in the cleavage sites in these peptides are explained by differences in the specificities of the proteinase subsite S2 and/or in their preference for Arg or Lys residues. The three tetrapeptides were not substrates for plasmin.
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D010450:Endopeptidases / Q000378:metabolism*; D006736:Horses; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D051381:Rats; D012697:Serine Endopeptidases; D013045:Species Specificity; D013379:Substrate Specificity; D013552:Swine; D014357:Trypsin / Q000378:metabolism*
D009842:Oligopeptides; D010450:Endopeptidases; D007610:Kallikreins; D012697:Serine Endopeptidases; D014357:Trypsin