Inhibition of trypsin-like serine proteinases by tripeptide arginyl and lysyl chloromethylketones.
Tripeptide derivatives of lysyl or arginyl chloromethylketone inhibit the trypsin-like serine proteases trypsin, thrombin, plasmin, Factor Xa, urokinase, tissue-type plasminogen activator and protein Ca following the reaction scheme: (formula; see text) Extremely potent tripeptide inhibitors were obtained for thrombin and trypsin (k2/Ki greater than 10(6) M-1s-1), moderate inhibitors for plasmin and Factor Xa (10(6) M-1s-1 greater than k2/Ki greater than 10(4) M-1s-1) and only weak inhibitors for urokinase, tissue-type plasminogen activator and protein Ca (k2/Ki less than 10(4) M-1s-1). Thrombin and Factor Xa as well as urokinase and tissue-type plasminogen activator can be discriminated on the basis of their inhibitory spectrum towards some of these inhibitors.
D000590:Amino Acid Chloromethyl Ketones; D055598:Chemical Phenomena; D002621:Chemistry; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D006801:Humans; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors; D015849:Plasminogen Inactivators; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; D013917:Thrombin / Q000037:antagonists & inhibitors; D014361:Trypsin Inhibitors; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D000590:Amino Acid Chloromethyl Ketones; D015849:Plasminogen Inactivators; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D005170:Factor X; D010960:Plasminogen Activators; D012697:Serine Endopeptidases; D013917:Thrombin; D015951:Factor Xa; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator