Structural analysis of the binding of the diquaternary pyridophenazine derivative dqdppn to B-DNA oligonucleotides.

The interaction of the ethylene-bipyridyldiylium-naphthaphenazine dication, dqdppn, with several hexa- and octanucleotide duplexes has been studied using CD and NMR. Taken together, these studies reveal that with the hexanucleotide, dqdppn intercalates into the terminal base pair, and causes a large twisting of the terminal base pair. In contrast, with all three octanucleotides, dqdppn intercalates more centrally within the sequence. The NMR-derived structures of two of the binding complexes demonstrate that dqdppn intercalates from the major groove in an unusual 'side-on' geometry, rather than threading through the helix. An analysis of these results indicates that the preferred binding site is not sequence-specific, but primarily at the most conformationally flexible DNA step.