Design, Sythesis and Biological Evaluation of Polyphenol-α-helical Peptide Conjugates as Potent HIV-1 Fusion Inhibitors

作者：Cheng Siqi; Liang Guodong; Jiang Xifeng; Wang Chao^*; Liu Keliang^*

来源：Chemical Journal of Chinese Universities, 2016, 37(7): 1287-1292.

DOI：10.7503/cjcu20160295

• Human immunodificiency virus type 1 (HIV-1)
• Fusion inhibitor
• alpha-Helical peptide
• Polyphenol

De novo-designed peptide sequences with an alpha-helical conformation can prevent fusogenic gp41 six. helical bundle (6HB) formation by specifically interacting with the Human Immunodificiency virus type 1 (HIV-1) gp41 N-terminal heptad repeat (NHR) region, thus inhibiting HIV-1-cell membrane fusion. Mean-while, polyphenols, such as hydroxytyrosol (HT) and (-)-epigallocatechin gallate (EGCG), are a major group of natural compounds with a broad spectrum of antiviral activity. In this paper, mHT were designed and obtained based on 3,4-dihydroxymethylacetic acid. Then, mHT and other bioactive polyphenols, were covalently conjugated to a certain alpha-helical peptide through specific linkers with different lengths and flexibilities. These conjugates interacted with the gp41 NHR region and exhibited promising fusion inhibitory activity, with IC50 values in the low micromolar range. This study provides a promising strategy for the development of fusion inhibitors against viruses with class I fusion proteins.

• 出版日期2016-7-10
• 单位沈阳药科大学; 中国人民解放军军事医学科学院