Effect of nucleobase change on cytosine deamination through DNA photo-cross-linking reaction via 3-cyanovinylcarbazole nucleoside.

Photo-chemical deamination of cytosine using 3-cyanovinylcarbazole nucleoside (K) mediated photo-cross-linking is a technique for site-directed mutagenesis. Using this technique in vivo requires the elimination of a high-temperature incubation step; instead, incubation should be carried out under physiological conditions. To improve the reactivity of K mediated photo-cross-link induced deamination of cytosine under physiological conditions, an evaluation of base pairing in cytosine was carried out with respect to its deamination. Guanine was replaced with 4 different counter bases (inosine, 2-aminopurine, 5-nitroindole, and nebularine), showing distinct hydrogen bonding patterns with target cytosine, which was incorporated at the -1 position with respect to K in the K-modified photo-responsive oligodeoxyribonucleotides to ascertain the role of hydrogen bonding in deamination under physiological conditions. Among the counter bases, inosine showed the highest acceleration towards the photo-induced deamination reaction.