8‐Oxo‐7,8‐Dihydroguanine can Improve Aptamer Affinity Toward Argininamide and its Selective Oxidation Promotes Crosslinks Formation

The effects of the substitution of a guanine (G) base by the oxidative lesion 8-oxo-7,8-dihydroguanine (OG) on the affinity of the DNA aptamer selected against L-argininamide (L-Rm) are studied. Results indicate that, depending on the position of the modified base located in the recognition site, the substitution of only one G by OG could either reduce, not affect, or increase such an affinity. In addition, attempts are carried out to promote chemical crosslinks between the aptamer and its target following selective oxidation of OG. Results show that such crosslinks could be produced with a high efficacy through nucleophilic addition of L-argininamide, presumably onto the C5 position of the oxidized OG base inserted into the aptamer in any position, and that no crosslink is generated for the original aptamer (not containing any OG). However, such reaction being very efficient, crosslinks are also produced between L-argininamide and oligonucleotides (including scramble sequences) that are not supposed to bind to that amino acid. Such an effect could be explained by the electrostatic interactions between the negatively charged oligonucleotides and the protonated amino acid, which favor the formation of crosslinks upon OG oxidation. Efforts to decrease formation of such nonspecific crosslinks are only partly successful.