Phosphorus-containing inhibitors of angiotensin-converting enzyme.
- 1 April 1982
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 79 (7) , 2176-2180
- https://doi.org/10.1073/pnas.79.7.2176
Abstract
Several phosphonamides, phosphoramides and phosphates having the general structure R-Y-P(O)(OH)-X-CH(CH3)-CO-Pro were synthesized and tested for inhibition of angiotensin-converting enzyme (dipeptidyl carboxypeptidase; peptidyldipeptide hydrolase). Inhibition depended on the nature of R, Y, and X such that the maximal effect was observed when X = NH, Y = CH2, and R = .vphi.CH2 (50% inhibition at 7 nM). Substitution of CH2 or O at X and O at Y produced significantly less potent inhibitions. Groups shorter or longer than R = .vphi.CH2 led to less active inhibitors, presumably due to nonoptimal interaction of the side chain with the S1 subsite.This publication has 18 references indexed in Scilit:
- Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acidsBiochemistry, 1977
- A crystallographic study of the complex of phosphoramidon with thermolysin. A model for the presumed catalytic transition state and for the binding of extended substratesJournal of Molecular Biology, 1977
- Possible Role of Renin in Hypertension as Suggested by Renin-Sodium Profiling and Inhibition of Converting EnzymeNew England Journal of Medicine, 1977
- A general transesterification method for the synthesis of mixed trialkyl phosphatesJournal of the American Chemical Society, 1977
- Studies on inhibitory effect of phosphoramidon and its analogs on thermolysinArchives of Biochemistry and Biophysics, 1975
- Pulmonary angiotensin-converting enzyme. Structural and catalytic properties.Journal of Biological Chemistry, 1975
- An Angiotensin Converting-Enzyme Inhibitor to Identify and Treat Vasoconstrictor and Volume Factors in Hypertensive PatientsNew England Journal of Medicine, 1974
- Inhibition of angiotensin-converting enzyme by analogs of peptides fromBothrops jararaca venomCellular and Molecular Life Sciences, 1973
- A THERMOLYSIN INHIBITOR PRODUCED BY ACTINOMYCETES: PHOSPHORAMIDONThe Journal of Antibiotics, 1973
- Synthese von Oligo‐ und Polynucleotiden, XVI. Synthese von Desoxyoligonucleotiden mit der Trichloräthyl‐PhosphatschutzgruppeEuropean Journal of Inorganic Chemistry, 1968