Highly potent and specific inhibitors of human renin.
FEBS Lett
; 220(2): 299-301, 1987 Aug 17.
Article
en En
| MEDLINE
| ID: mdl-3111889
ABSTRACT
We have designed and synthesized a series of small peptides containing a perfluoroalkyl ketone group at the C-terminal position of the angiotensin I sequence as inhibitors of human renin. From this series of compounds, 8 and 10 showed strong inhibition of human renin (IC50 = 3 X 10(-9), 7 X 10(-9) M, respectively). Compound 10 did not inhibit pepsin and cathepsin D at 10(-4) M. Comparison of the IC50 of compound 8 and compound 11 (8.7 X 10(-7) M) demonstrated the marked effect of the perfluoropropyl group on the potency of inhibition on renin, presumably due to the strong electron-withdrawing effect causing the ketone in 8 to exist predominantly as the hydrate--thus mimicking the tetrahedral transition state during hydrolysis of the scissile Leu10--Val11 amide bond.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Renina
/
Inhibidores Enzimáticos
Límite:
Humans
Idioma:
En
Revista:
FEBS Lett
Año:
1987
Tipo del documento:
Article