Base pairing of 8-oxoguanosine and 8-oxo-2'-deoxyguanosine with 2'-deoxyadenosine, 2'-deoxycytosine, 2'-deoxyguanosine, and thymidine.

Abstract

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-A 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) approximately dGWC.dC > 8-OxodGH.dG (8-OxoGH.dG) > 8-OxodGH.dA (8-OxoGH.dA) > 8-OxodGH.dThd (8-oxoGH.dThd) approximately 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.