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Highly potent and specific inhibitors of human renin.

Authors
  • Sham, H L
  • Stein, H
  • Rempel, C A
  • Cohen, J
  • Plattner, J J
Type
Published Article
Journal
FEBS Letters
Publisher
Wiley (John Wiley & Sons)
Publication Date
Aug 17, 1987
Volume
220
Issue
2
Pages
299–301
Identifiers
PMID: 3111889
Source
Medline
License
Unknown

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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