BIOMAT Database Logo BIOMAT Database Logo

Renin inhibitors. Free-Wilson and correlation analysis of the inhibitory potency of a series of pepstatin analogues on plasma renin. 1987

D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
SANOFI Recherche, Montpellier, France.

Free-Wilson and correlation analysis were combined to study a series of 34 pepstatin analogues in which mainly position 2 was varied. A statistically highly significant correlation was found between the inhibitory activity of the analogues on an enriched plasma renin preparation and structural parameters of the amino acid side chain in position 2. The crucial parameters were found to be the NMR chemical shift of the alpha-carbon, the localized electrical (inductive) effect, and the van der Waals radius related steric parameter, which demonstrated the dominating influence of electronic inductive effects compared to steric bulk. The model gives insight into the structural requirements for effective inhibition and suggests the histidine-2 derivative, a positive outlier in this series, as a lead compound for further structure-activity studies.

UI MeSH Term Description Entries
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D010436 Pepstatins N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.
D012044 Regression Analysis Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable. Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
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
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

Related Publications

D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
Pepstatin analogues as novel renin inhibitors.
July 1986, Journal of medicinal chemistry,
D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
Renin inhibitory effect of N-acetyl-pepstatin.
February 1978, Japanese journal of pharmacology,
D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
Kinetics of the inhibitory effect of pepstatin on the reaction of hog renin with rat plasma substrate.
July 1974, Circulation research,
D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
Pepstatin inhibition of proteinase-free human renin.
January 1982, Enzyme,
D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
Proceedings: Studies on the inhibitory effect of pepstatin on the renin--angiotensinogen reaction.
January 1974, Naunyn-Schmiedeberg's archives of pharmacology,
D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
Synthesis and renin inhibitory properties of a new soluble pepstatin derivative.
January 1980, Journal of cardiovascular pharmacology,
D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
Renin inhibitors. Dipeptide analogues of angiotensinogen utilizing a dihydroxyethylene transition-state mimic at the scissile bond to impart greater inhibitory potency.
December 1988, Journal of medicinal chemistry,
D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
Inhibition of human plasma renin activity by pepstatin.
December 1976, The Journal of clinical endocrinology and metabolism,
D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
Plasma renin concentration: comparison of angiotensinase inhibitors and correlation with plasma renin activity and aldosterone.
May 1974, The Journal of laboratory and clinical medicine,
D Nisato, and J Wagnon, and G Callet, and D Mettefeu, and J L Assens, and C Plouzane, and B Tonnerre, and V Pliska, and J L Fauchère
A pepstatin-immunometric assay for active renin in human plasma.
June 1988, Clinica chimica acta; international journal of clinical chemistry,
Copied contents to your clipboard!