Inhibitory Effects of ω-Guanidino Acid Esters on Trypsin, Plasmin, Thrombin and Plasma Kallikrein

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Abstract
Various esters of ω-guanidino acids were prepared, and their inhibitory effects on trypsin [EC 3.4.4.4], plasmin [EC 3.4.4.14], thrombin [EC 3.4.4.13] and plasma kallikrein [EC 3.4.4.21] were studied. The protective effects of hexyl esters of various ω-guanidino acids on the inactivation of trypsin by diisopropylphosphofluoridate (DFP) were examined. Among the hexyl esters of ω-guanidinocapric, δ-guanidinovaleric and γ-guanidinobutyric acid examined, hexyl δ-guanidinovalerate was the most effective inhibitor of tryptic and plasmin activities. The inhibitory effect of hexyl δ-guanidinovalerate on trypsin was competitive. These three hexyl esters protected trypsin from inactivation by DFP. Various esters of δ-guanidinovaleric acid caused extensive inhibition of the caseinolytic and esterolytic activities of trypsin and plasmin, and the order of their effects was hexyl>butyl>isobutyl ester. The esterolytic activity of trypsin on hexyl δ-guanidinovalerate was very small, and that of plasmin was negligible. Hexyl δ-guanidinovalerate and ω-guanidinocaproate showed extensive inhibitory effects on the esterase activity of plasma kallikrein, although the inhibitory effect of hexyl γ-guanidinobutyrate was low. The hexyl, butyl and isobutyl esters of δ-guanidinovalerate had almost the same inhibitory effects. Hexyl δ-guanidinovalerate inhibited plasma kallikrein competitively. Hexyl ω-aminocaproate which is a strong inhibitor of trypsin and plasmin did not inhibit the esterolytic activity of plasma kallikrein. Hexyl δ-guanidinovalerate did not inhibit the esterolytic activity of thrombin but instead increased its activity to 120 per cent at 4mM concentration.

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