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- Title
SYNTHESIS AND DOCKING STUDIES OF RENIN INHIBITORS CONTAINING ESTER AND AMIDE DERIVATIVES OF (3S, 4S)-4-AMINO-HYDROXY ACIDS WITH S<sub>3</sub>-S<sub>3</sub>' RENIN BINDING SITE.
- Authors
WINIECKA, IWONA; MARSZAŁEK, DOROTA; JAWORSKI, PAWEŁ; MAZUREK, ANDRZEJ; PĘCAK, PAULINA; WINIECKI, KAJETAN; WIERZBOWSKI, ARTUR
- Abstract
Seven novel potential renin inhibitors, having a structure based on the peptide fragment 8-13 of human angiotensinogen - a natural substrate for renin, have been designed and synthesized. All peptides were obtained by the carbodiimide method in solution and purified by chromatography on the SiO2 column. In P1-P3' positions, they contain esters or N-alkyl amides of modified (3S, 4S)-4-amino-3-hydroxyacids. The achieved inhibitory activity IC50 was of 10-6-10-7M Inhibitory activity of the compounds was measured in vitro by high-performance liquid chromatography (HPLC) determination of lowering the concentration of substrate in the presence of renin and the potential rennin inhibitor. Their resistance to enzymatic degradation was assayed by the determination of stability against chymotrypsin activity. Their hydrophobicity evaluated as a Log P-value was calculated by a computer method. The theoretical binding affinity of thus obtained inhibitors was elaborated based on docking to the S3-S3' pocket of the renin active site.
- Subjects
RENIN; ANGIOTENSINOGEN; CHROMATOGRAPHIC analysis; HIGH performance liquid chromatography; BINDING sites
- Publication
Acta Poloniae Pharmaceutica, 2021, Vol 78, Issue 1, p55
- ISSN
0001-6837
- Publication type
Article
- DOI
10.32383/appdr/132280