PNNL

Abstract

Products of riboflavin-mediated photosensitization of 2’-deoxyguanosine (dG) and thymidylyl-(39-59)-29-deoxyguanosine (TpdG) by 350-nm light in oxygen-saturated aqueous solution have been isolated and identified as 1-(2-deoxy-ß–D-erythro- pentofuranosyl) oxaluric acid (ß-dOx) and thymidylyl- (39-59)-1-(2-deoxy-ß-D-erythro-pentofuranosyl) oxaluric acid (Tpß-dOx), respectively. In aqueous solution the modified ß-deoxyribonucleoside is slowly converted to the a-anomer, generating a-dOx and Tp a-dOx. These modified nucleosides and dinucleoside monophosphates have been isolated by HPLC and characterized by proton and carbon NMR spectroscopy, fast atom bombardment mass spectrometry, and enzymatic analyses. Both a-dOx and Tpa-dOx slowly convert back into the modified ß-deoxyribonucleoside, indicating that the furanosidic anomers are in dynamic equilibrium. Relative to TpdG, the rate of hydrolysis of Tpß-dOx and Tpa-dOx by spleen phosphodiesterase is greatly reduced. Hot piperidine (1.0 M, 908C, 30 min) destroys TpßdOx and Tpa-dOx. Riboflavin-mediated photosensitization of TpdG in D2O instead of H2O has no detectable effect on the yield of Tpß-dOx, suggesting that oxaluric acid is generated through a Type-I reaction mechanism, likely through the intermediary on initially generated 8-oxo-7,8-dihydro-29-deoxyguanosine.