PROTEASE-INHIBITORY ACTIVITIES OF LEUPEPTIN ANALOGUES

Abstract

Thirty analogues of leupeptin were synthesized and examined for their inhibitory activities against trypsin, papain, plasmin, kallikrein, thrombin and urokinase in vitro. Benzoyland α-naphthalenesulfonyl-L-leucyl-L-argininal were 8 times more inhibitory to papain, benzyloxycarbonyl-L-pyroglutamyl-L-leucyl-L-argininal 10 times more to trypsin and plasmin, and DL-2-pipecolyl-L-leucyl-L-argininal 25 times more to kallikrein than leupeptin. Against urokinase, only L-pyroglutamyl-L-leucyl-L-argininal exhibited a potent inhibitory activity. α-Naphthalenesulfonyl-, dansyl- and benzyloxycarbonyl-(2S, 3R)-3-ammo-2-hydroxy-4-phenylbutyryl-L-leucyl-L-argininal were inhibitory to thrombin.