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 du...

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Bibliographic Details
Published in:Journal of biological inorganic chemistry 2006-10, Vol.11 (7), p.824-834
Main Authors: Morgan, Joy L, Buck, Damian P, Turley, Adam G, Collins, J Grant, Keene, F Richard
Format: Article
Language:English
Subjects:
Adenine - chemistry
Adenine - metabolism
Base Sequence
Binding Sites
DNA - chemistry
DNA - metabolism
Intercalating Agents - chemistry
Ligands
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Sequence Data
Molecular Structure
Oligonucleotides - chemistry
Oligonucleotides - metabolism
Organometallic Compounds - chemistry
Phenanthrolines - chemistry
Pyridines - chemistry
Pyrimidines - chemistry
Ruthenium - chemistry
Spectrometry, Fluorescence
Stereoisomerism
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Summary: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.
ISSN:0949-8257