Independent generation of the 5-hydroxy-5,6-dihydrothymidin-6-yl radical and its reactivity in dinucleoside monophosphates - PubMed (original) (raw)

. 2004 Oct 20;126(41):13287-97.

doi: 10.1021/ja048492t.

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Independent generation of the 5-hydroxy-5,6-dihydrothymidin-6-yl radical and its reactivity in dinucleoside monophosphates

Qibin Zhang et al. J Am Chem Soc. 2004.

Abstract

Hydroxyl radical is a major reactive oxygen species produced by gamma-radiolysis of water or Fenton reaction. It attacks pyrimidine bases and gives the 5-hydroxy-5,6-dihydropyrimidin-6-yl radical as the major product. Here we report the synthesis of all four stereoisomers of 5-hydroxy-6-phenylthio-5,6-dihydrothymidine (T*), which, upon 254 nm UV irradiation, give rise to the 5-hydroxy-5,6-dihydrothymidin-6-yl radical (I). We also incorporated the photolabile radical precursors into dinucleoside monophosphates d(GT*) and d(TT*) and characterized major products resulting from the 254-nm irradiation of these dinucleoside monophosphates. Our results showed that, under anaerobic conditions, the most abundant product emanating from the 254-nm irradiation of d(GT*) and d(TT*) is an abasic site lesion. Products with the thymine portion being modified to thymine glycol and 5-hydroxy-5,6-dihydrothymine were also observed. In addition, we demonstrated that radical I can attack the C8 carbon atom of its 5' neighboring guanine and give rise to a novel cross-link lesion. Moreover, LC-MS/MS results showed that gamma-radiation of d(GT) under anaerobic condition yielded the same type of cross-link lesions.

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