Potent and selective inhibitors of an aspartyl protease-like endothelin converting enzyme identified in rat lung
| Autor: | Gerard M. Sullivan, C. A. Marselle, T. W. von Geldern, Jinshyun R. Wu-Wong, Kazumi Shiosaki, A. S. Tasker, T. J. Opgenorth, B. K. Sorensen |
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| Rok vydání: | 1993 |
| Předmět: |
Molecular Sequence Data
Cathepsin D Blood Pressure Endothelin-Converting Enzymes Plasma renin activity Structure-Activity Relationship chemistry.chemical_compound In vivo Pepstatins Renin Drug Discovery Animals Aspartic Acid Endopeptidases Humans Protease Inhibitors Amino Acid Sequence Amino Acids Lung Cathepsin chemistry.chemical_classification Molecular Structure biology Endothelins Cell Membrane Metalloendopeptidases Water Endothelin 1 Rats Enzyme Solubility chemistry Biochemistry Enzyme inhibitor biology.protein Molecular Medicine Pepstatin |
| Zdroj: | Journal of Medicinal Chemistry. 36:468-478 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Two structurally distinct series of potent and selective inhibitors of an aspartyl protease-like endothelin converting enzyme (ECE) activity identified in the rat lung have been developed. Pepstatin A, which potently inhibits the rat lung ECE, served as the basis for the first series. Alternatively, selected renin inhibitors containing the dihydroxyethylene moiety were shown to be inhibitors of rat lung activity. Subsequent modifications improved inhibition of the rat lung ECE while eliminating renin activity. Both series of ECE inhibitors demonstrated a range of selectivity over Cathepsin D. Water-solubilizing moieties were appended onto selected compounds to facilitate in vivo testing. Partial reduction of the pressor response to exogenously administered Big ET-1 was observed with selected rat lung ECE inhibitors. |
| Databáze: | OpenAIRE |
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