Independent generation of the 5-hydroxy-5,6-dihydrothymidin-6-yl radical and its reactivity in dinucleoside monophosphates.
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.
Department of Chemistry-027, University of California at Riverside, Riverside, California 92521-0403, USA.
Qibin
Q
Zhang
Yinsheng
Y
Wang
D004247:DNA / Q000737:chemistry* / Q000528:radiation effects*; D015226:Dinucleoside Phosphates / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry / Q000528:radiation effects; D010100:Oxygen / Q000737:chemistry; D010777:Photochemistry; D013237:Stereoisomerism; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000528:radiation effects; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry
D015226:Dinucleoside Phosphates; D005609:Free Radicals; C029389:thymine glycol; D004247:DNA; D013941:Thymine; D010100:Oxygen; D013936:Thymidine