Synthesis and triplex-forming ability of oligonucleotides bearing 1-substituted 1H-1,2,3-triazole nucleobases

Using the copper(I)-catalyzed alkyne-azide 1,3-dipolar cycloaddition, a post-elongation modification of 1-ethynyl substituted nucleobases has been employed to construct 18 variations of oligonucleotides from a common oligonucleotide precursor. The triplex-forming ability of each oligonucleotide with dsDNA was evaluated by the UV melting experiment. It was found that triazole nucleobases generally tend to exhibit binding affinities in the following order: CG>TA>AT, GC base pairs. Among the triazole nucleobases examined, a 1-(4-ureidophenyl)triazole provided the best result with regard to affinity and selectivity for the CG base pair.