Design,synthesis and activity evaluation of novel peptide fusion inhibitors targeting HIV-1 gp41

• 作 者: JianjunTan;MinSu;YiZeng;CunxinWang;
• 机 构: College of Life Science and Bioengineering.Beijing University of Technology,Beijing 100124,China
• 出 处: 第八届国际分子模拟与信息技术应用学术会议
• 发表日期: 2016年期

　　Human immunodeficiency virus type 1(HIV-1),the pathogen of acquired immunodeficiency syndrome(AIDS),causes about 2 million people to death every year.Fusion inhibitors targeted the envelope prolein(gp41)represent a novel and alternative approach for anti-AIDS therapy,which terminates the HIV-1 life cycle at an early stage.Using CPG21-652 as a template,a series of peptides were designed,synthesized and evaluated in vitro assays.An interesting phenomenon was found that the substitution of hydrophobic residues at solvent accessibly sites could increase the anti-HIV activity when the C-terminal sequence was extended with an enough numbers of amino acids.After the active peptides was synthesized and evaluated,peptide 8 showed the best anti-HIV-1 ⅢB whole cell activity(MAGI IC50 = 53.02 nM).Further study indicated that peptide 8 bound with the gp41 NHR helix,and then blocked the conformation of 6-helix,thus inhibited virus-cell membrane fusion.The results would be helpful for the design of peptide fusion inhibitors against HIV-1 infection.