Right-Handed Alternating DNA Conformation: Poly(dA-dT) Adopts the Same Dinucleotide Repeat with Cesium, Tetraalkylammonium, and 3α ,5β ,17β -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 3α , 17β -dipyrrolidin-1′-yl-5β -Δ9,11-androstene dimethiodide (3α ,5β ,17β -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 3α ,5β ,17β -dipyrandenium bound to poly(dA-dT) at low binding ratios induces a switch to the dinucleotide repeat conformation at adjacent steroidfree duplex regions. This observation contrasts with a previous demonstration that the diastereoisomeric 3β ,5α ,17β -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 (ZDNA) 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.