Bioorganic & medicinal chemistry letters, 2006, Vol.16 (1), p.40-43
2006
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- Autor(en) / Beteiligte
- Titel
- Peptide inhibitors of dengue virus NS3 protease. Part 2: SAR study of tetrapeptide aldehyde inhibitors
- Ist Teil von
- Bioorganic & medicinal chemistry letters, 2006, Vol.16 (1), p.40-43
- Ort / Verlag
- Oxford: Elsevier Ltd
- Erscheinungsjahr
- 2006
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- With the aim of discovering potent and selective dengue NS3 protease inhibitors, we systematically synthesized and evaluated a series of tetrapeptide aldehydes based on lead aldehyde 1 (Bz-Nle-Lys-Arg-Arg-H, K i = 5.8 μM). In general, we observe that interactions of P 2 side chain are more important than P 1 followed by P 3 and P 4. Tripeptide and dipeptide aldehyde inhibitors also show low micromolar activity. Additionally, an effective non-basic, uncharged replacement of P 1 Arg is identified. With the aim of discovering potent and selective dengue NS3 protease inhibitors, we systematically synthesized and evaluated a series of tetrapeptide aldehydes based on lead aldehyde 1 (Bz-Nle-Lys-Arg-Arg-H, K i = 5.8 μM). In general, we observe that interactions of P 2 side chain are more important than P 1 followed by P 3 and P 4. Tripeptide and dipeptide aldehyde inhibitors also show low micromolar activity. Additionally, an effective non-basic, uncharged replacement of P 1 Arg is identified.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-894XeISSN: 1464-3405DOI: 10.1016/j.bmcl.2005.09.049Titel-ID: cdi_proquest_miscellaneous_70194093
- Format
- –
- Schlagworte
- Aldehydes - antagonists & inhibitors, Antibiotics. Antiinfectious agents. Antiparasitic agents, Antiviral agents, Binding, Competitive, Biological and medical sciences, Boronic Acids - chemistry, Chemistry, Pharmaceutical - methods, Dengue Virus - enzymology, Dengue virus NS3 protease, Dose-Response Relationship, Drug, Drug Design, Enzyme Inhibitors - pharmacology, Hydrogen Bonding, Ketones - chemistry, Kinetics, Medical sciences, Models, Chemical, Models, Molecular, Peptide inhibitors, Peptides - chemistry, Peptides - pharmacology, Pharmacology. Drug treatments, Protease Inhibitors - chemistry, Protease Inhibitors - pharmacology, Protein Binding, RNA Helicases - antagonists & inhibitors, RNA Helicases - chemistry, Serine Endopeptidases - chemistry, Structure-Activity Relationship, Substrate Specificity, Time Factors, Viral Nonstructural Proteins - antagonists & inhibitors, Viral Nonstructural Proteins - chemistry