Strategy on screening fluorescent guanine analogues to specifically detect 5-carboxylcytosine adduct

Abstract The adduct 5-carboxylcytosine (5caC), one of the products involved in demethylation pathway, has the potential to serve as a target for specifically deciphering proteins that regulate gene expression and chromatin organization. The fluorescence detection with its ultra-high sensitivity can break through the limitations of traditional detection methods and achieve single molecule detection of 5caC. In this work, the guanine analogue Gr 3 with large π-conjugation and large Stokes shift (89.25 nm) is selected as the fluorescence probe to specifically recognize and monitor 5caC. Because of its bright fluorescence when paired with C and a complete fluorescence quenching when paired with 5caC, this on-off switching feature of Gr 3 stems from excited-state intermolecular charge transfer. Furthermore, it is found that after linking with deoxyribose, this discriminative function remains unchanged. This strategy could contribute to detect the presence of 5caC in the genetic material, and thus prevent diseases associated with this epigenetic modification.