| Abstract: | Human plasma kallikreins (EC 3.4.21.8) were purified as three distinct enzyme entities which hydrolyzed arginine esters and were active in releasing kinin from heated human plasma as measured by guinea pig ileum contraction bio-assay. The three enzymatically active fractions were termed as 19 S, 7 S-I and 7 S-II kallikreins. They represented purifications of 262- 2200- and 110-fold, respectively. These enzyme activities showed differences in physicochemical and biochemical properties as it appears from their elution profile on Sephadex G-200 and DEAE-cellulose columns, affinity for substrates and susceptibility of inhibition by various protease inhibitors such as trasylol and soya bean trypsin inhibitor. The data suggest that all these three enzyme preparations were most likely kallikreins. All these three enzymes (19 S, 7 S-I and 7 S-II) were inhibited by a series of amidino compounds competitively. Diamidines consisting of two amidinophenyl residues linked in para position by molecular bridge were comparatively stronger inhibitors of all of three enzymes than those linked in meta position and those having single ring structure. The possibility that some of these amidino compounds might prove to be useful for treatment of disease states where the kallikrein-kinin system plays a role, is discussed. |
