Specific inhibitor of puromycin-sensitive aminopeptidase with a homophthalimide skeleton: identification of the target molecule and a structure-activity relationship study.
2-(2,6-Diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (2: PIQ-22) was found to be a potent and specific inhibitor of puromycin-sensitive aminopeptidase (PSA). Lineweaver-Burk plot analysis showed that PSA is inhibited by PIQ-22 in a non-competitive manner. Structure -activity relationship studies indicated that tautomerism of the imidobenzoylketone group in the cyclic imide moiety of the PIQ-22 skeleton is important for the inhibitory activity.
Komoda
M
M
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Kakuta
H
H
Takahashi
H
H
Fujimoto
Y
Y
Kadoya
S
S
Kato
F
F
Hashimoto
Y
Y
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D011691:Puromycin / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007546:Isoquinolines; C400282:N-(2,6-diethylphenyl)homophthalimide; D011691:Puromycin; D000626:Aminopeptidases