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N-(alpha-Hydroxyalkanoyl) derivatives of Leu-Val-Phe-OCH3 as inhibitors of renin. 1980

R L Johnson

The following N-(alpha-hydroxylakanoyl) derivatives of Leu-Val-Phe-OCH3 were synthesized and tested for their ability to inhibit human amniotic renin: D- and L-alpha-hydroxyisocaproyl-Leu-Val-Phe-OCH3, D- and L-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3, L-2-hydroxy-3-phenylpropanoyl-Leu-Val-Phe-OCH3, and D- and L-alpha-hydroxyphenylacetyl-Leu-Val-Phe-OCH3. Analysis of the compounds through the use of Dixion plots showed all of the compounds to be competitive inhibitors of renin. All but D-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3 were found to be more active than the known tetrapeptide inhibitor Leu-Leu-Val-Phe-OCH3 (1). The two most active compounds of the series were L-alpha-hydroxyisocaproyl-Leu-Val-Phe-OCH3 (Ki = 0.23 mM) and L-alpha-hydroxyisovaleryl-Leu-Val-Phe-OCH3 (Ki = 0.3 mM).

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D011863 Radioimmunoassay Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. Radioimmunoassays
D012083 Renin A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19. Angiotensin-Forming Enzyme,Angiotensinogenase,Big Renin,Cryorenin,Inactive Renin,Pre-Prorenin,Preprorenin,Prorenin,Angiotensin Forming Enzyme,Pre Prorenin,Renin, Big,Renin, Inactive
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000650 Amnion The innermost membranous sac that surrounds and protects the developing embryo which is bathed in the AMNIOTIC FLUID. Amnion cells are secretory EPITHELIAL CELLS and contribute to the amniotic fluid. Amniotic Membrane,Amnions,Amniotic Membranes,Membrane, Amniotic,Membranes, Amniotic
D000803 Angiotensin I A decapeptide that is cleaved from precursor angiotensinogen by RENIN. Angiotensin I has limited biological activity. It is converted to angiotensin II, a potent vasoconstrictor, after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME.
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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