Selectivity at a three-base bulge site in the DNA binding of DeltaDelta-[{Ru(phen)2} 2(mu-dppm)]4+ [dppm is 4,6-bis(2-pyridyl)pyrimidine; phen is 1,10-phenanthroline].
The binding of the stereoisomers of [{Ru(phen)2}2(mu-bpm)]4+, [{Ru(phen)2}2(mu-dppm)]4+ and [{Ru(phen)2}2(mu-bb)]4+ {phen is 1,10-phenanthroline; bpm is 2,2'-bipyrimidine, dppm is 4,6-bis(2-pyridyl)pyrimidine, bb is 1,2-bis[4-(4'-methyl-2,2'-bipyridyl)]ethane} to an oligonucleotide duplex [d(GCATCGAAAGCTACG).d(CGTAGCCGATGC)] containing a three-base bulge has been studied using a fluorescence intercalator displacement assay. Of the dinuclear ruthenium complexes, the dppm-linked species showed the strongest binding to the oligonucleotide, with the DeltaDelta isomer binding slightly more strongly than the meso isomer and the LambdaLambda isomer exhibiting the weakest binding. In order to determine whether the DeltaDelta-[{Ru(phen)2}2(mu-dppm)]4+ metal complex specifically bound at the three-base bulge site, a 1H NMR study of the binding of the metal complex to the oligonucleotide duplex d(GCATCGAAAGCTACG)*d(CGTAGCCGATGC) was carried out. Although a detailed picture of the metal complex-oligonucleotide association could not be determined from the NMR results owing to the broadening of the resonances from the metal complex and nucleotide residues at the bulge site, the NMR results do indicate that the metal complex specifically binds at the three-base bulge site. The combined results of this study suggest that the dppm-bridged dinuclear ruthenium complexes have considerable potential as probes for the unusual secondary structure obtained by the insertion of a three-base bulge within duplex DNA.
Morgan
Joy L
JL
Department of Chemistry, School of Pharmacy & Molecular Sciences, James Cook University, Townsville, QLD, 4811, Australia.
Buck
Damian P
DP
Turley
Adam G
AG
Collins
J Grant
JG
Keene
F Richard
FR
D000225:Adenine / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D007364:Intercalating Agents / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry*; D010618:Phenanthrolines / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism
C515399:4,6-bis(2-pyridyl)pyrimidine; D007364:Intercalating Agents; D008024:Ligands; D009841:Oligonucleotides; D009942:Organometallic Compounds; D010618:Phenanthrolines; D011725:Pyridines; D011743:Pyrimidines; C515400:mu-(4,6-bis(2-pyridyl)pyrimidine)bis(1,10-phenanthroline)ruthenium(IV); D012428:Ruthenium; D004247:DNA; D000225:Adenine; C025205:1,10-phenanthroline