DNA Redox Reactions

Methods to study oxidative damage in DNA may lead to a better understanding of DNA damage in vivo as well as provide insights about the mechanism(s) of charge transfer through different media. Currently, the effects of distance, sequence, structure, and energetics on reaction rate and product(s) formation are being investigated. One method to initiate a redox reaction in DNA and study

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charge transfer and O2

o2/H2O

Piperidine

Scheme 6. Photoinduced oxidative damage of DNA.

guanine oxidation is to use a photoinduced trigger. A number of organic72-76 and inorganic18,21'23,55'77 triggers covalently attached or intercalated in DNA are being explored.

Henderson et al. describe the use of an anthraquinone (AQ)-linked DNA duplex containing four separate GG blocks to probe long-range guanine oxidation.25 As illustrated in Scheme 6, irradiation of the tethered anthraquinone at 350 nm

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generates anthraquinone radical anion and an adjacent base radical cation.25'78'79 This radical cation then migrates through DNA until it is trapped by the 5'-guanine of a GG block to yield an 8-oxoguanine in the presence of O2/H2O. Subsequent hot piperidine treatment cleaves DNA at the oxidized guanine site and the resulting shorter DNA strands are analyzed by polyacrylamide gel electrophoresis to compare GG cleavage efficiency with different distances. Long-range charge transfer can occur over distances of approximately 200 A.

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