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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 78; no. 7; pp. 4063 - 4067
• Main Authors: Patel, D J, Kozlowski, S A, Suggs, J W, Cox, S D
• Format: Journal Article
• Language: English
• Published: United States National Acad Sciences 01.07.1981
• Subjects: Androstenes; Cations; Cesium; DNA; Hydrogen Bonding; Ligands; Magnetic Resonance Spectroscopy; Nucleic Acid Conformation; Poly dA-dT; Polydeoxyribonucleotides; Quaternary Ammonium Compounds; Stereoisomerism; Steroids, Heterocyclic; Structure-Activity Relationship
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.78.7.4063

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.