Fluorescent Nucleobase Analogues with Extended Pi Surfaces Stabilize DNA Duplexes Containing O6‐Alkylguanine Adducts

Abstract

Chemical alkylation of DNA produces potentially toxic and mutagenic damage such as O6‐alkylguanine (O6‐alkylG) adducts. Non‐natural nucleoside analogues that pair with DNA adducts provide a potential basis for studying damaged DNA. Herein, we evaluated the base pairing properties of elongated nucleoside analogues containing napthalene‐derived tricyclic nucleobases as DNA adduct‐pairing nucleoside analogues in DNA hybridization probes. DNA duplex melting studies revealed that the elongated nucleoside analogs formed more stable base pairs opposite O6‐alkylG than G and were better able to distinguish between G, O6‐alkylG, and an abasic site than any previously described nucleoside analogue. DNA duplexes containing an elongated base analogue exhibited different fluorescence intensities when paired opposite O6‐alkylG vs. G or abasic sites. Their selectivity for stabilizing alkylated DNA make the elongated hydrophobic base analogues improved candidates for incorporating into DNA hybridization probes targeting O6‐alkylG.