title: DNA Triplex-Based Complexes Display Anti-HIV-1-Cell Fusion Activity.
abstract: DNA triplexes with hydrophobic modifications were designed and evaluated for their activity as inhibitors of the cell fusion of human immunodeficiency virus type 1 (HIV-1). Triplex inhibitors displayed low micromolar activities in the cell-cell fusion assay and nanomolar activities in the anti-HIV-1 pseudovirus test. Helix structure and the presence of sufficient numbers of hydrophobic regions were essential for the antifusion activity. Results from native polyacrylamide gel electrophoresis and a fluorescent resonance energy transfer-based inhibitory assay indicated that these triplexes may interact with the primary pocket at the glycoprotein 41 (gp41) N-heptad repeat, thereby inhibiting formation of the HIV-1 gp41 6-helical bundle. Triplex-based complexes may represent a novel category of HIV-1 inhibitors in anti-HIV-1 drug discovery.
authors.affiliation: 1 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology , Beijing, China .
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: 1 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology , Beijing, China .
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: 1 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology , Beijing, China .
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xu
authors.affiliation: 2 Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, China .
authors.forename: Huihui
authors.initials: H
authors.lastname: Chong
authors.affiliation: 1 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology , Beijing, China .
authors.forename: Wenqing
authors.initials: W
authors.lastname: Lai
authors.affiliation: 1 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology , Beijing, China .
authors.forename: Xifeng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: 1 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology , Beijing, China .
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: 2 Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, China .
authors.forename: Yuxian
authors.initials: Y
authors.lastname: He
authors.affiliation: 1 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology , Beijing, China .
authors.forename: Keliang
authors.initials: K
authors.lastname: Liu
mesh_terms: D020816:Amino Acid Motifs; D001681:Biological Assay; D002459:Cell Fusion; D002461:Cell Line, Transformed; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D031541:Fluorescence Resonance Energy Transfer; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D015700:HIV Envelope Protein gp41; D009838:Oligodeoxyribonucleotides; C051802:triplex DNA; D004247:DNA