Right-handed alternating DNA conformation: poly(dA-dT) adopts the same dinucleotide repeat with cesium, tetraalkylammonium, and 3 alpha, 5 beta, 17 beta-dipyrrolidinium steroid dimethiodide cations in aqueous solution.
We demonstrate that poly(dA-dT) can adopt two conformations in solution, with the relative proportions dependent on the nature and concentration of the counter ion and cationic ligands. The synthetic DNA exhibits a dinucleotide repeat conformation on addition of CsF and Me4NCl at molar concentrations, with the NMR spectral changes reflecting a common conformational change at one glycosidic torsion angle and one phosphodiester linkage. We also observe the same dinucleotide repeat in the neighbor-exclusion 3 alpha, 17 beta-dipyrrolidin-1'-yl-5 beta- delta 9,11-androstene dimethiodide (3 alpha, 5 beta, 17 beta-dipyrandenium) complex, with the steroid diammonium ligand binding in the groove of the stacked poly(dA-dT) duplex and the complex stabilized through the interaction of one of the charged ends with the backbone phosphate. We demonstrate further that 3 alpha, 5 beta, 17 beta-dipyrandenium bound to poly(dA-dT) at low binding ratios induces a switch to the dinucleotide repeat conformation at adjacent steroid-free duplex regions. This observation contrasts with a previous demonstration that the diastereoisomeric 3 beta, 5 alpha, 17 beta-dipyrandium binds to poly(dA-dT) by partial insertion between unstacked tilted base pairs. The NMR parameters rule out a left-handed alternating DNA structure (Z DNA) for the observed poly(dA-dT) dinucleotide repeat conformation, but right-handed alternating DNA models are under consideration. The facile interconversion of poly(dA-dT) between two conformations, one of which exhibits a dinucleotide repeat and can be induced by ligand binding, may provide a mechanism for the recognition of specific nucleic acid sequences by DNA-binding proteins.
D000736:Androstenes; D002412:Cations; D002586:Cesium; D004247:DNA; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D011067:Poly dA-dT; D011089:Polydeoxyribonucleotides; D000644:Quaternary Ammonium Compounds; D013237:Stereoisomerism; D013260:Steroids, Heterocyclic; D013329:Structure-Activity Relationship
D000736:Androstenes; D002412:Cations; D008024:Ligands; D011089:Polydeoxyribonucleotides; D000644:Quaternary Ammonium Compounds; D013260:Steroids, Heterocyclic; D002586:Cesium; D011067:Poly dA-dT; C031962:3,17-dipyrrolidin-1'-yl-5-delta(9,11)-androstene dimethiodide; D004247:DNA; C027917:tetramethylammonium