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.
Waywell
Philip
P
Dept. of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK.
Thomas
James A
JA
Williamson
Mike P
MP
D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009942:Organometallic Compounds; D010619:Phenazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*
D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; D010619:Phenazines; D004247:DNA