Discovery of potent anilide inhibitors against the severe acute respiratory syndrome 3CL protease
| Autor: | Jim-Min Fang, Chih-Jung Kuo, Chun-Hung Lin, Tun-Hsun Kuo, Yin-Ta Wu, Wen-Bin Yang, Hung-Jyun Huang, Jiun-Ling Chen, Chi-Huey Wong, Jiun-Jie Shie, Po-Huang Liang |
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| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Stereochemistry Protein Conformation medicine.medical_treatment Peptide Tripeptide Severe Acute Respiratory Syndrome Antiviral Agents Structure-Activity Relationship Viral Proteins Drug Discovery Endopeptidases medicine Structure–activity relationship Anilides Protease Inhibitors Coronavirus 3C Proteases chemistry.chemical_classification Protease biology Tetrapeptide Active site Cysteine Endopeptidases Kinetics Enzyme chemistry Biochemistry Severe acute respiratory syndrome-related coronavirus Enzyme inhibitor biology.protein Molecular Medicine |
| Zdroj: | Journal of medicinal chemistry. 48(13) |
| ISSN: | 0022-2623 |
| Popis: | A diversified library of peptide anilides was prepared, and their inhibition activities against the SARS-CoV 3CL protease were examined by a fluorogenic tetradecapeptide substrate. The most potent inhibitor is an anilide derived from 2-chloro-4-nitroaniline, l-phenylalanine and 4-(dimethylamino)benzoic acid. This anilide is a competitive inhibitor of the SARS-CoV 3CL protease with K(i) = 0.03 muM. The molecular docking experiment indicates that the P1 residue of this anilide inhibitor is distant from the nucleophilic SH of Cys145 in the active site. |
| Databáze: | OpenAIRE |
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