Meso-[{Ru(phen)2}2(mu-bpm)]4+: A high-affinity DNA bulge probe {bpm - 2,2'-bipyrimidine; phen = 1,10-phenanthroline}

Morgan, Joy L., Buck, Damian P., Turley, Adam G., Collins, J. Grant, and Keene, F. Richard (2006) Meso-[{Ru(phen)2}2(mu-bpm)]4+: A high-affinity DNA bulge probe {bpm - 2,2'-bipyrimidine; phen = 1,10-phenanthroline}. Inorganica Chimica Acta, 359 (3). pp. 888-898.

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The binding of the stereoisomers of [{Ru(Me2bpy)2}2(μ-bpm)]4+, [{Ru(phen)2}2(μ-bpm)]4+ and [{Ru(Me2phen)2}2(μ-bpm)]4+ (Me2bpy = 4,4′-dimethyl-2,2′-bipyridine; bpm = 2,2′-bipyrimidine; phen = 1,10-phenanthroline; Me2phen = 4,7-dimethyl-1,10-phenanthroline) to a tridecanucleotide d(CCGAGAATTCCGG)2 which contains a single adenine bulge site, and four control dodecanucleotides, have been studied using a fluorescence intercalator displacement (FID) assay. The meso isomer of [{Ru(phen)2}2(μ-bpm)]4+ showed the strongest binding to the bulge-containing tridecanucleotide. In order to gain a greater understanding of the basis of the higher affinity exhibited by the meso isomer towards the bulge sequence, a 1H NMR study of the binding of the two enantiomers (ΔΔ and ΛΛ) of rac-[{Ru(phen)2}2(μ-bpm)]4+, and the, meso (ΔΛ) diastereoisomer, to the tridecanucleotide d(CCGAGAATTCCGG)2 was carried out. The NMR results suggest that the meso isomer binds selectively at the bulge site in the tridecanucleotide minor groove, but closer to the 3′-direction and with less structural perturbations of the groove than the ΔΔ and ΛΛ isomers. The results of this study confirm that dinuclear ruthenium complexes have excellent potential as DNA bulge probes, and meso-[{Ru(phen)2}2(μ-bpm)]4+ in particular has a high affinity (1 × 106 M−1) and selectivity for a single adenine bulge site.

Item ID: 4586
Item Type: Article (Research - C1)
ISSN: 1873-3255
Keywords: DNA bulges; bulge probes; NMR spectroscopy; fluorescence intercalator displacement assay; ruthenium; dinuclear; dinuclear ruthenium(II) complexes;
Date Deposited: 15 Jun 2009 01:38
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 100%
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