title: The use of hairpin DNA duplexes as HIV-1 fusion inhibitors: synthesis, characterization, and activity evaluation.
abstract: Discovery of new drugs for the treatment of AIDS that possess unique structures associated with novel mechanisms of action are of great importance due the rapidity with which drug-resistant HIV-1 strains evolve. Recently we reported on a novel class of DNA duplex-based HIV-1 fusion inhibitors modified with hydrophobic groups. The present study describes a new category of hairpin fusion inhibitor DNA duplexes bearing a 3 nucleotide loop located at either the hydrophobic or hydrophilic end. The new loop structures were designed to link 2 separate duplex-forming oligodeoxynucleotides (ODNs) to make helix-assembly easier and more thermally stable resulting in a more compact form of DNA duplex based HIV-1 fusion inhibitors. A series of new hairpin duplexes were tested for anti-HIV-1 cell-cell membrane fusion activity. In addition, Tm, CD, fluorescent resonance energy transfer assays, and molecular modeling analyses were carried out to define their structural activity relationships and possible mechanisms of action.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xu
authors.affiliation: MOE Key Laboratory of Structure-Based Drug Design & Discovery, Shenyang Pharmaceutical University, 103 Wenhua Rd, Shenhe District, Shenyang 110016, China.
authors.forename: Baohua
authors.initials: B
authors.lastname: Zheng
authors.affiliation: MOE Key Laboratory of Structure-Based Drug Design & Discovery, Shenyang Pharmaceutical University, 103 Wenhua Rd, Shenhe District, Shenyang 110016, China.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Cai
authors.affiliation: MOE Key Laboratory of Structure-Based Drug Design & Discovery, Shenyang Pharmaceutical University, 103 Wenhua Rd, Shenhe District, Shenyang 110016, China. Electronic address: mscheng@263.com.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China. Electronic address: keliangliu55@126.com.
authors.lastname: Keliang Liu
mesh_terms: D031541:Fluorescence Resonance Energy Transfer; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009692:Nucleic Acid Heteroduplexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D023581:HIV Fusion Inhibitors; D009692:Nucleic Acid Heteroduplexes; D009838:Oligodeoxyribonucleotides
keywords: Fusion inhibitor; HIV-1; Hairpin DNA duplex; Loop domain