8-oxoguanine is a common oxidation product in DNA.  The metallointercalator Ru(phen)2dppz2+ is a guanine-selective oxidizing agent via the flash-quench technique. Here, we introduce its osmium analogue as a way to selectively oxidize 8-oxoguanine in double-stranded DNA. , as visualized by DNA-protein crosslinking. With a 3+/2+ couple of 1.15 V,  Os(phen)2dppz3+ should be able to oxidize 8-oxo-G (~0.7 V) without oxidizing guanine (~1.3V). In plasmid containing 8-oxo-G, flash-quench treatment with Os(phen)2dppz2+ and Co(NH3)5Cl2+ leads to crosslinking with histone in gel shift experiments. Furthermore, in gel shift experiments with a duplex of the oligonucleotide 5'-ATATGATAT8GATATGATATto -3' (8 = 8-oxo-G), flash-quench treatment with Ru(phen)2dppz2+ in the presence of histone produces a band of intermediate mobility (presumably 1:1 crosslink) and well-shifted material. In contrast, analogous treatment with Os(phen)2dppz2+ produces only the band of intermediate mobility, consistent with the presence of only a single site that is oxidizable by the osmium complex.

8-Oxoguanine oxidation and production in duplex DNA

245th National Meeting (2013)

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