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Anti-HIV Activities of Intramolecular G4 and Non-G4 Oligonucleotides.
- Source :
-
Nucleic acid therapeutics [Nucleic Acid Ther] 2017 Feb; Vol. 27 (1), pp. 56-66. Date of Electronic Publication: 2016 Oct 20. - Publication Year :
- 2017
-
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.
- Subjects :
- Aptamers, Nucleotide chemical synthesis
Aptamers, Nucleotide genetics
Binding Sites
Cell Proliferation drug effects
Cell Survival drug effects
DNA chemistry
Dose-Response Relationship, Drug
G-Quadruplexes
Humans
Jurkat Cells
Molecular Docking Simulation
Molecular Dynamics Simulation
Nucleic Acid Conformation
Phosphorothioate Oligonucleotides chemical synthesis
Phosphorus Compounds chemistry
Promoter Regions, Genetic genetics
Proto-Oncogene Proteins c-bcl-2 genetics
Structure-Activity Relationship
Aptamers, Nucleotide chemistry
Aptamers, Nucleotide pharmacology
HIV Infections therapy
HIV-1 drug effects
Phosphorothioate Oligonucleotides chemistry
Phosphorothioate Oligonucleotides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2159-3345
- Volume :
- 27
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nucleic acid therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 27763826
- Full Text :
- https://doi.org/10.1089/nat.2016.0624