A novel 2'-F,4'-C-OMe⁻arabinouridine (araU) was successfully synthesized and introduced into oligonucleotides. The oligonucleotide containing 2'-F,4'-C-OMe⁻araU exhibited improved nuclease resistance and RNA hybridizing selective ability relative to 2'-F⁻araU. In particular, when 2'-F,4'-C-OMe⁻araU inserted into C⁻H⋯F⁻C bonding-favorable 5'⁻uridine⁻purine⁻3' steps, the modified oligonucleotide showed remarkable binding affinity and selectivity to RNA complements. Thus, 2'-F,4'-C-OMe⁻araU has valuable antisense properties and can be used as novel chemical modification for antisense therapeutic strategy.
Keywords: arabinonucleotide; chemical modification; fluorine; pseudohydrogen bond.