Anti-HIV Activities of Intramolecular G4 and Non-G4 Oligonucleotides

• Published in: Nucleic acid therapeutics Vol. 27; no. 1; pp. 56 - 66
• Main Authors: Prokofjeva, Maria, Tsvetkov, Vladimir, Basmanov, Dmitry, Varizhuk, Anna, Lagarkova, Maria, Smirnov, Igor, Prusakov, Kirill, Klinov, Dmitry, Prassolov, Vladimir, Pozmogova, Galina, Mikhailov, Sergey N.
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.02.2017
• Subjects: Aptamers, Nucleotide - chemical synthesis; Aptamers, Nucleotide - chemistry; Aptamers, Nucleotide - genetics; Aptamers, Nucleotide - pharmacology; Binding Sites; Brief Communication; Cell Proliferation - drug effects; Cell Survival - drug effects; Deoxyribonucleic acid; DNA; DNA - chemistry; Dose-Response Relationship, Drug; G-Quadruplexes; HIV; HIV Infections - therapy; HIV-1 - drug effects; Human immunodeficiency virus; Humans; Jurkat Cells; Lentivirus; Molecular biology; Molecular Docking Simulation; Molecular Dynamics Simulation; Nucleic Acid Conformation; Phosphorothioate Oligonucleotides - chemical synthesis; Phosphorothioate Oligonucleotides - chemistry; Phosphorothioate Oligonucleotides - pharmacology; Phosphorus Compounds - chemistry; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins c-bcl-2 - genetics; Retroviridae; Structure-Activity Relationship; Topology; inhibition; HIV; aptamer; phosphorothioate; lentivirus
• ISSN: 2159-3337; 2159-3345; 2159-3345
• DOI: 10.1089/nat.2016.0624

New natural and chemically modified DNA aptamers that inhibit HIV-1 activity at submicromolar concentrations (presumably via preventing viral entry into target cells) are reported. The new DNA aptamers were developed based on known intramolecular G-quadruplexes (G4s) that were functionally unrelated to HIV inhibition [the thrombin-binding aptamer and the fragment of the human oncogene promoter ( Bcl2 )]. The majority of previously described DNA inhibitors of HIV infection adopt intermolecular structures, and thus their folding variability represents an obvious disadvantage. Intramolecular architectures refold correctly after denaturation and are generally easier to handle. However, whether the G4 topology or other factors account for the anti-HIV activity of our aptamers is unknown. The impact of chemical modification (thiophosphoryl internucleotide linkages) on aptamer activity is discussed. The exact secondary structures of the active compounds and further elucidation of their mechanisms of action hopefully will be the subjects of future studies.