Base Pairing of 8-Oxoguanosine and 8-Oxo-2′-deoxyguanosine with 2′-Deoxyadenosine, 2′-Deoxycytosine, 2′-Deoxyguanosine, and Thymidine

Base pair formation between O-silyl derivatives of 8-oxoguanosine (8-OxoG) and 8-oxo-2′-deoxyguanosine (8-OxodG) with 2′-deoxyadenosine (dA), 2′-deoxycytosine (dC), 2′-deoxyguanosine (dG), and thymidine (dThd) have been examined by NMR methods in chloroform. 8-OxoG and 8-OxodG form base pairs with all four nucleosides, suggesting that they can mimic the base pairing properties of any DNA base. In 8-OxodG·dA or 8-OxoG·dA base pairs both bases assume Hoogsteen geometry with respect to both bases. Hoogsteen and Watson-Crick base pairs are formed between 8-OxodG or 8-OxoG and either dThd or dG. Only Watson–Crick geometry is seen for 8-OxodG·dC and 8-OxoG·dC base pairs. In all base pairs the glycosidic bond of 8-OxodG or 8-OxoG is syn and anti for the base pair partner. Additional base pairing studies with the modified nucleosides 1-methyl-8-oxoguanosine (1-Me-8-oxoG), 7-methyl-8-oxoguanosine (7-Me-8-oxoG), and 8-methoxyguanosine (8-OMeG), modified nucleosides structurally related to 8-OxoG and 8-OxodG, support the proposed base pair structures and aided in the determination of base pair geometry. Association constants were determined for 8-OxoG·dN and 8-OxodG·dN (N = A. C., G, Thd) base pairs as well as the normal dThd·dA and dG·dC base pairs. The magnitude of the association constants allows the relative stabilities of the base pairs to be determined: 8-OxodGWC·dC (8-OxoGWC·dC) ≈= dGWC·dC > 8-OxodGH·dG (8-OxoGH·dG) > 8-OxodGH·dA (8-OxoGH·dA) > 8-OxodGH·dThd (8-oxoGH·dThd) ≈ dThd·dA. The formation of these base pairs is consistent with the known mutagenic nature of 8-oxo-2′-deoxyguanosine and with NMR studies of oligonucleotides containing the 8-oxoG modification.