1. Conjugation of a NonspecificAntiviral Sapogenin with a Specific HIV Fusion Inhibitor: A PromisingStrategy for Discovering New Antiviral Therapeutics.
- Author
-
Wang, Chao, Lu, Lu, Na, Heya, Li, Xiangpeng, Wang, Qian, Jiang, Xifeng, Xu, Xiaoyu, Yu, Fei, Zhang, Tianhong, Li, Jinglai, Zhang, Zhenqing, Zheng, Baohua, Liang, Guodong, Cai, Lifeng, Jiang, Shibo, and Liu, Keliang
- Subjects
- *
SAPOGENINS , *BIOACTIVE compounds , *TRITERPENES , *ANTIVIRAL agents , *HIV fusion inhibitors , *DRUG development , *STRUCTURE-activity relationship in pharmacology , *CHIMERIC proteins - 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]
- Published
- 2014
- Full Text
- View/download PDF