Design of antiviral stapled peptides containing a biphenyl cross-linker
| Autor: | Francesca Curreli, Avinash Muppidi, Qing Lin, Nan Li, Asim K. Debnath, Hongtao Zhang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Anti-HIV Agents
Clinical Biochemistry Pharmaceutical Science Peptide Microbial Sensitivity Tests Biochemistry Article Cell Line Protein–protein interaction Structure-Activity Relationship Viral entry Drug Discovery Humans Structure–activity relationship Surface plasmon resonance Molecular Biology chemistry.chemical_classification Dose-Response Relationship Drug Chemistry Biphenyl Compounds Organic Chemistry Isothermal titration calorimetry Biphenyl compound Cross-Linking Reagents Capsid Drug Design HIV-1 Molecular Medicine Peptides |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 24:1748-1751 |
| ISSN: | 0960-894X |
| Popis: | Here we report the design and synthesis of a panel of stapled peptides containing a distance-matching biphenyl cross-linker based upon a peptide capsid assembly inhibitor reported previously. Compared with the linear peptide, the biphenyl-stapled peptides exhibited significantly enhanced cell penetration and potent antiviral activity in the cell-based infection assays. Isothermal titration calorimetry and surface plasmon resonance experiments revealed that the most active stapled CAI peptide binds to the C-terminal domain of HIV capsid protein as well as envelop glycoprotein gp120 with low micromolar binding affinities, and as a result, inhibits both the HIV-1 virus entry and the virus assembly. |
| Databáze: | OpenAIRE |
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