title: Anti-HIV Activities of Intramolecular G4 and Non-G4 Oligonucleotides.
abstract: 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.
authors.affiliation: 1 Engelhardt Institute of Molecular Biology RAS , Moscow, Russia .
authors.forename: Maria
authors.initials: M
authors.lastname: Prokofjeva
authors.affiliation: 2 Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency , Moscow, Russia .|3 Topchiev Institute of Petrochemical Synthesis Russian Academy of Sciences , Moscow, Russia .
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tsvetkov
authors.affiliation: 2 Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency , Moscow, Russia .
authors.forename: Dmitry
authors.initials: D
authors.lastname: Basmanov
authors.affiliation: 1 Engelhardt Institute of Molecular Biology RAS , Moscow, Russia .|2 Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency , Moscow, Russia .
authors.forename: Anna
authors.initials: A
authors.lastname: Varizhuk
authors.affiliation: 2 Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency , Moscow, Russia .
authors.forename: Maria
authors.initials: M
authors.lastname: Lagarkova
authors.affiliation: 2 Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency , Moscow, Russia .
authors.forename: Igor
authors.initials: I
authors.lastname: Smirnov
authors.affiliation: 2 Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency , Moscow, Russia .
authors.forename: Kirill
authors.initials: K
authors.lastname: Prusakov
authors.affiliation: 2 Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency , Moscow, Russia .|4 Moscow Institute of Physics and Technology (State University) , Moscow Region, Russia .
authors.forename: Dmitry
authors.initials: D
authors.lastname: Klinov
authors.affiliation: 1 Engelhardt Institute of Molecular Biology RAS , Moscow, Russia .
authors.forename: Vladimir
authors.initials: V
authors.lastname: Prassolov
authors.affiliation: 2 Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency , Moscow, Russia .
authors.forename: Galina
authors.initials: G
authors.lastname: Pozmogova
authors.affiliation: 1 Engelhardt Institute of Molecular Biology RAS , Moscow, Russia .
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Mikhailov
mesh_terms: D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D054856:G-Quadruplexes; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D054735:Phosphorothioate Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017553:Phosphorus Compounds / Q000737:chemistry; D011401:Promoter Regions, Genetic / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D052157:Aptamers, Nucleotide; C000595707:BCL2 protein, human; D054735:Phosphorothioate Oligonucleotides; D017553:Phosphorus Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; C081676:thrombin aptamer; D004247:DNA
keywords: HIV; aptamer; inhibition; lentivirus; phosphorothioate