Inhibitory effects of ω-amino and ω-guanidino acid esters on the first component of human complement

Abstract

Various esters of ω-amino and ω-guanidino acids are strong inhibitors for trypsin-like enzymes, such as trypsin, plasmin, plasma kallikrein and thrombin. The inhibitory effects of these esters on the esterase of the first component of complement (C1-esterase), the conversion of C1 to C1-esterase and hemolysis by complement were examined. Aromatic esters of ε-guanidinocaproic acid and trans-4-aminomethylcyclohexanecarboxylic acid (AMCHA) caused strong, competitive inhibition of C1-esterase. However, p-aminophenyl β-phenylpropionate, which strongly inhibits chymotrypsin, had no effect on C1-esterase, although this enzyme hydrolyzes ethyl N α- acetyl- l-tyrosinate preferentially to methyl N α- tosyl- l-argininate . This suggests that the active center of C1-esterase resembles those of trypsin-like enzymes rather than that of chymotrypsin. Moreover, aromatic esters of ε-guanidinocaproic acid and AMCHA strongly inhibited the conversion of C1 to C1-esterase. The strongest inhibitor was the phenyl ester of ε-guanidinocaproic acid and it caused great retardation of hemolysis by the complement reaction. This retardation by the phenyl ester seemed to be due to its inhibition of formation of the EA-C1-C4 intermediate from EA-C1 (EA = antibody-sensitized erythrocytes).