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 ε-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 ε-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 ε-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.
