alpha.-DNA, a single-stranded secondary structure stabilized by ionic and hydrogen bonds: d(A+-G)n

A novel nucleic acid secondary structure, exemplified by d(A+-G)lo, is formed by an intramolecular, cooperative, acid-induced, coil - helix transition. The helix is apparently left-handed, lacks base stacking and pairing, and is maintained by hydrogen and ionic bonds between dA+ "side- chain" residues (with electropositive hydrogens -N6H2, -N,+H) and the phosphodiester backbone. Modeling indicates that those dA+ residues lie approximately parallel to the helix axis, interacting with the n - 1 backbone phosphates (with electronegative oxygens), somewhat like the -C=O-H-N- longitudinal interactions in a protein a-helix. Moreover, the intervening dG side-chain residues are extrahelical, as are amino acid side chains of an a-helix. All currently recognized types of nucleic acid secondary structure involve helical stacks of bases. Such stacks occur in single strands, in base pairs of hairpins formed by single strands, in base pairs of two-stranded complexes, in base triplets of three-stranded structures, and in base quartets of four-stranded complexes. In this paper, we provide details of an entirely different type of nucleic acid helical secondary structure, one that does not depend for its stabilization on helically wound stacks of bases or base pairs. Rather, this novel type of secondary structure encompasses single strands of the repeating ho- mopurine doublet sequence d(A-G),, helically twisted by an unusual combination of ionic and hydrogen (H) bonds essentially parallel to the helix axis. We first came upon this nucleic acid secondary structure in the course of investigating the molecular properties of d(A- G)lo, which displays an intense differential absorption of circularly polarized light (CD) without concomitant develop- ment of hypochromism in the near-ultraviolet (UV) when the pH is reduced from neutrality. Additional observations enabled attribution of this unusual dichotomy in optical properties to a single-stranded helical secondary structure stabilized largely by Coulombic interactions between nega- tively charged backbone phosphates and distal protonated dA (dA+) residues that do not overlap with their nearest neighbor dG residues. Although these properties made it possible to deduce some regular features of the secondary structure of d(A+-G)lo, direct evidence for many structural ~