In vitro inhibition of human renin by statine-containing tripeptide renin inhibitor (ES-1005).
Dipeptide and tripeptide derivatives containing a statine residue were synthesized as human renin inhibitors. ES-305, bis[(1-naphthyl)methyl]acetyl-histidyl-statine-2(S)-methylbutylami de, was found to be a highly potent human renin inhibitor that is species-specific and enzyme-specific. The replacement of the methylbutylamide of ES-305 with the leucyl-lysinol (ES-1005) showed similar high potency against human renin (Ki value of 2.4 x 10(-9) M) and monkey renin (Ki value of 7.9 x 10(-9) M) as ES-305. ES-1005 competitively inhibited human renin. The compound was about one order of magnitude less potent against pig, dog, and rabbit renins. It had moderate inhibitory potencies against cathepsin D and pepsin (IC50 of cathepsin D and pepsin of 1.6 x 10(-5) and 8.0 x 10(-6) M, respectively). ES-1005, a newly synthesized tripeptide derivative containing statine, is a highly potent inhibitor of not only primate renin but also a wide variety of nonprimate renins.
Kokubu
T
T
2nd Department of Internal Medicine, Ehime University School of Medicine, Japan.
Hiwada
K
K
Murakami
E
E
Muneta
S
S
Morisawa
Y
Y
Yabe
Y
Y
Koike
H
H
Iijima
Y
Y
D000818:Animals; D004285:Dogs; D006041:Goats; D000882:Haplorhini; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology*; D011480:Protease Inhibitors; D011817:Rabbits; D051381:Rats; D013552:Swine; D000092502:Renin Inhibitors
D009842:Oligopeptides; D011480:Protease Inhibitors; D000092502:Renin Inhibitors; C056080:ES 1005