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New fluoroketones as human renin inhibitors
Author(s) -
Tarnus Céline,
Jung Michel J.,
Rémy Jean-Marc,
Baltzer Sylvie,
Schirlin Daniel G.
Publication year - 1989
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(89)80012-2
Subject(s) - tripeptide , chemistry , stereochemistry , residue (chemistry) , ketone , amide , hydrolysis , peptide , peptide bond , renin–angiotensin system , dipeptide , enzyme , renin inhibitor , biochemistry , organic chemistry , biology , blood pressure , endocrinology
Renin inhibition has been evaluated for a new class of fluorinated ketones, true analogues of peptides that have been retroinverted at the C‐terminal position. The readily formed hydrate of the ketone is proposed to mimic the tetrahedral intermediate that occurs during the enzyme‐catalyzed hydrolysis of amide linkage. From this series of compounds it appears that the number of reverted amide bonds is crucial in terms of activity. Furthermore, a shortening of the C‐terminal part of our peptide analogues and the replacement of the leucine residue in P 1 by a cyclohexylalanine leads to the tripeptide analogue 12 a potent renin inhibitor (IC 50 = 3.5 × 10 −9 M).