Reactivity between acetone and single-stranded DNA containing a 5′-capped 2′-fluoro-N7-methyl guanine

DNA-mediated catalysis is an emerging field in bioorganic chemistry and chemical biology. However, the functional group diversity and known reactivity of DNA (A, T, C, and G) is relatively limited in scope. This relatively defined reactivity can limit the utility of DNA as a catalyst. In an effort to expand the functional group diversity and chemical reactivity of DNA, we sought to explore reactions involving single-stranded DNA equipped with a stabilized variant of N7-methyl guanine (2′-fluoro-5′-N7-methyl guanine). Here, we show that 5′-capped 2′-fluoro-N7-methyl guanine-labeled single-stranded DNA reacts with a ketone to afford a ketone-labeled DNA. This reaction likely proceeds through a reactive ylide or N-heterocyclic carbene. Taken together, our findings suggest that 2′-fluoro-5′-N7-methyl guanine is a stable adduct that can be selectively incorporated into ssDNA and functionalized with a ketone moiety by reaction with a simple ketone. Incorporation of this nucleoside into ssDNA may be useful for the evolution of novel deoxyribozymes that catalyze new reactions, including those which proceed via a reactive ylide or N-heterocyclic carbene-mediated chemistry.