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Conjugation of a NonspecificAntiviral Sapogenin with a Specific HIV Fusion Inhibitor: A PromisingStrategy for Discovering New Antiviral Therapeutics.
- Source :
-
Journal of Medicinal Chemistry . Sep2014, Vol. 57 Issue 17, p7342-7354. 13p. - Publication Year :
- 2014
-
Abstract
- Triterpenesaponins are a major group of active components in natural productswith nonspecific antiviral activities, while T20 peptide (enfuvirtide),which contains a helix zone-binding domain (HBD), is a gp41-specificHIV-1 fusion inhibitor. In this paper, we report the design, synthesis,and structure–activity relationship (SAR) of a group of hybridmolecules in which bioactive triterpene sapogenins were covalentlyattached to the HBD-containing peptides via click chemistry. We foundthat either the triterpenes or peptide part alone showed weak activityagainst HIV-1 Env-mediated cell–cell fusion, while the hybridsgenerated a strong cooperative effect. Among them, P26–BApcexhibited anti-HIV-1 activity against both T20-sensitive and -resistantHIV-1 strains and improved pharmacokinetic properties. These resultssuggest that this scaffold design is a promising strategy for developingnew HIV-1 fusion inhibitors and possibly novel antiviral therapeuticsagainst other viruses with class I fusion proteins. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00222623
- Volume :
- 57
- Issue :
- 17
- Database :
- Academic Search Index
- Journal :
- Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 98249756
- Full Text :
- https://doi.org/10.1021/jm500763m