CYCLOGUO · Formation and roles of the 5',8-cyclo-2'-deoxyguanosine lesion""

Free radical attack to genetic material leads to damages that are involved in pathologies as well as in aging. Guanine is the preferred oxidation site of DNA, and 8-oxo-dG is used as marker of radical stress, with some drawbacks due to oxidative artefacts during the analysis. The project addresses the chemical biology of 5’,8-cyclo-2’-deoxyguanosine (5’,8-cyclo-dG), a tandem damage produced by free radical insult to the 5’ position of the sugar. The compound has an extra covalent bond between the base and sugar moieties and occurs as 5’S and 5’R diastereomers. Chemical studies on 5’,8-cyclo-dG, paralleled with 8-oxo-dG, are expected to contribute to a full scenario of guanine damage. The project addresses: i) Structure and reactivity features of the 5’,8-cyclo-dG formation and diastereomeric ratios as reporter of different DNA supramolecular organization and environmental factors