Synthesis of 8-oxo-7,8-dihydro-2′-deoxyguanosine from 2′-deoxyguanosine using Cu(II)/H2O2/ascorbate: A new strategy for an improved yield

Abstract

The free nucleoside 2′-deoxyguanosine (dGuo) is the most susceptible to oxidation by reactive oxygen species (ROS) compared to the other free nucleosides, and its oxidation product 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) has been used as a biomarker to quantify oxidative stress damage. We investigated different reactions using Fe2+ or Cu2+ and H2O2 in order to identify the reaction with the best yield. HPLC coupled with a UV detector and micrOTOF mass spectrometry were used to detect and confirm the identity of 8-oxodGuo. The optimized reaction synthesized 8-oxodGuo with a yield of 72.0%, much higher than that previously described in the literature. Our improved method for 8-oxodGuo synthesis could be extremely useful for assays that require the synthesis of internal standards labeled with stable isotopes.

Keywords

• dGuo
• 8-oxodGuo
• synthesis
• Fenton reaction
• DNA damage