Journal of Medicinal Chemistry p. 7342 - 7354 (2014)
Update date:2022-07-29
Topics: Conjugation Discovery Antiviral Strategy Fusion
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
Liu, Keliang
Triterpene saponins are a major group of active components in natural products with nonspecific antiviral activities, while T20 peptide (enfuvirtide), which contains a helix zone-binding domain (HBD), is a gp41-specific HIV-1 fusion inhibitor. In this paper, we report the design, synthesis, and structure-activity relationship (SAR) of a group of hybrid molecules in which bioactive triterpene sapogenins were covalently attached to the HBD-containing peptides via click chemistry. We found that either the triterpenes or peptide part alone showed weak activity against HIV-1 Env-mediated cell-cell fusion, while the hybrids generated a strong cooperative effect. Among them, P26-BApc exhibited anti-HIV-1 activity against both T20-sensitive and -resistant HIV-1 strains and improved pharmacokinetic properties. These results suggest that this scaffold design is a promising strategy for developing new HIV-1 fusion inhibitors and possibly novel antiviral therapeutics against other viruses with class I fusion proteins.
View MoreHefei EnliPharma Tecnology Co.,Ltd
Contact:0086-551-66399836
Address:Qing Cheng ShuiXiang Building 805, Mengcheng North Road , ShuangFeng Economic Development Zone Anhui HeFei
HANGZHOU YUNUO CHEMICAL CO.,LTD
website:http://www.yunuochem.com
Contact:0571-83715115
Address:hangzhou
Changsha Nutritopper Bio Technology Co.,Ltd.
Contact:+86-731-87803543
Address:East 1st Street, Baima Road, Ningxiang County
Guangzhou Chemical Reagent Factory
Contact:+86-20-8435 9820 or 8435 7345
Address:Southern Guangzhou, Guangdong, China
Contact:+86-731-84427351
Address:154 JIANXIANG SOUTH ROAD
Doi:10.1016/S0040-4020(01)87056-3
(1991)Doi:10.1016/j.cclet.2011.06.012
(2011)Doi:10.1021/jo00012a017
(1991)Doi:10.1002/ejoc.201500659
(2015)Doi:10.1021/jo201255z
(2011)Doi:10.1007/s10593-011-0787-z
(2011)