8-Oxoguanine Forms Quartets with a Large Central Cavity

[Image: see text] Oxidation of a guanine nucleotide in DNA yields an 8-oxoguanine nucleotide ((oxo)G) and is a mutagenic event in the genome. Due to different arrangements of hydrogen-bond donors and acceptors, (oxo)G can affect the secondary structure of nucleic acids. We have investigated base pairing preferences of (oxo)G in the core of a tetrahelical G-quadruplex structure, adopted by analogues of d(TG(4)T). Using spectroscopic methods, we have shown that G-quartets can be fully substituted with (oxo)G nucleobases to form an (oxo)G-quartet with a revamped hydrogen-bonding scheme. While an (oxo)G-quartet can be incorporated into the G-quadruplex core without distorting the phosphodiester backbone, larger dimensions of the central cavity change the cation localization and exchange properties.