title: 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. Benzoyl- and alpha-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. alpha-Naphthalensulfonyl-, dansyl- and benzyloxycarbonyl-(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucyl-L- argininal were inhibitory to thrombin.
authors.affiliation: Research Laboratories, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Saino
authors.forename: T
authors.initials: T
authors.lastname: Someno
authors.forename: S
authors.initials: S
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Aoyagi
authors.forename: H
authors.initials: H
authors.lastname: Umezawa
mesh_terms: D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D007610:Kallikreins / Q000037:antagonists & inhibitors; D007976:Leupeptins / Q000138:chemical synthesis* / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis*; D010206:Papain / Q000037:antagonists & inhibitors; D013917:Thrombin / Q000037:antagonists & inhibitors; D014361:Trypsin Inhibitors; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
chemical_list: D007976:Leupeptins; D009842:Oligopeptides; D014361:Trypsin Inhibitors; D007610:Kallikreins; D013917:Thrombin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D010206:Papain