Thrombin inhibition with dipeptidyl argininals.
Human alpha- and gamma-thrombins (with high and essentially no fibrinogen clotting activities, respectively) were inhibited in chromogenic substrate assays by the dipeptidyl argininals: antipain less than leupeptin less than H-D-Phe-Pro-argininal approximately Boc-D-Phe-Pro-argininal. In clotting assays with alpha-thrombin, I50 values were slightly higher than Ki values from chromogenic substrate assays, except for a somewhat lower I50 for antipain. Our data cautions the use of argininal proteinase inhibitors in the assessment of thrombin functions, and the high potency of H-D-Phe-Pro-argininal and its derivative suggest pharmaceutical applications.
Witting
J I
JI
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201.
Pouliott
C
C
Catalfamo
J L
JL
Fareed
J
J
Fenton
J W
JW
D000976:Antipain / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors*
D007976:Leupeptins; D009842:Oligopeptides; D000976:Antipain; C035202:H-D-Phe-Pro-arginal; C030798:tert-butyloxycarbonyl-phenylalanyl-prolyl-arginal; D013917:Thrombin; C032854:leupeptin