Kinetic study on the mechanism of inhibition of trypsin and trypsin-like enzymes by p-guanidinobenzoate ester.
It was found that [4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate]methanesulfonate (E-3123) inhibits trypsin, thrombin and kallikrein, and its inhibitory activity is most potent toward trypsin. The interactions of these enzymes with E-3123 were studied mainly by using stopped-flow spectrophotometry. E-3123 behaved as a quasi-substrate of the enzymes and the inhibitory property was due to the efficient production of the stable acyl-enzyme. The acylation process with trypsin was exceedingly effective, and the resulting acyl-enzyme was the most stable among the three enzymes tested. This observation affords a rational basis for explaining the action of E-3123, which is a transient inhibitor most active toward trypsin.
Nochi
S
S
Shimomura
N
N
Hattori
T
T
Sato
T
T
Miyake
Y
Y
Tanizawa
K
K
D006146:Guanidines / Q000138:chemical synthesis / Q000494:pharmacology*; D007700:Kinetics; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; C057059:4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate