title: Design, synthesis and activity evaluation of novel peptide fusion inhibitors targeting HIV-1 gp41.
abstract: 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 protein (gp41) represent a novel and alternative approach for anti-AIDS therapy, which terminates the HIV-1 life cycle at an early stage. Using CP621-652 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 accessible 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.
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China. Electronic address: tanjianjun@bjut.edu.cn.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Tan
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Cunxin
authors.initials: C
authors.lastname: Wang
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000821:virology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015700:HIV Envelope Protein gp41 / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D015700:HIV Envelope Protein gp41; D010455:Peptides; C514787:gp41 protein, Human immunodeficiency virus 1
keywords: Drug design; Fusion inhibitors; HIV-1; Peptide; gp41