Identification of the α and β anomers of 1-(2-deoxy-D-erythro- pentofuranosyl)-oxaluric acid at the site of riboflavin-mediated photooxidation of guanine in 2′-deoxyguanosine and thymidylyl-3′-5′- deoxyguanosine

Article abstract of DOI:10.1562/2005-06-01-RA-562

Products of riboflavin-mediated photosensitization of 2′- deoxyguanosine (dG) and thymidylyl-(3′-5′)-2′-deoxyguanosine (TpdG) by 350-nm light in oxygen-saturated aqueous solution have been isolated and identified as 1-(2-deoxy-β-erythro-pentofuranosyl) oxaluric acid (β-dOx) and thymidylyl-(3′-5′)-1-(2-deoxy-β-D-erythro- pentofuranosyl) oxaluric acid (Tpβ-dOx), respectively. In aqueous solution the modified β-deoxyribonucleoside is slowly converted to the α-anomer, generating α-dOx and Tpα-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 α-dOx and Tpα-dOx slowly convert back into the modified β-deoxyribonucleoside, indicating that the furanosidic anomers are in dynamic equilibrium. Relative to TpdG, the rate of hydrolysis of Tpβ-dOx and Tpα-dOx by spleen phosphodiesterase is greatly reduced. Hot piperidine (1.0 M, 90°C, 30 min) destroys Tpβ-dOx and Tpα-dOx. Riboflavin-mediated photosensitization of TpdG in D ₂O instead of H₂O has no detectable effect on the yield of Tpβ-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-2′-deoxyguanosine.