Stable Recognition of TA Interruptions by Triplex Forming Oligonucleotides Containing a Novel Nucleoside^†

We have prepared the 2‘-aminoethoxy derivative of the S nucleoside (^2AES) and incorporated it into triplex-forming oligonucleotides for recognition of TA interruptions within a target oligopurine tract. Fluorescence melting, UV melting, and DNase I footprinting experiments show that ^2AES has greater affinity than G or S for a single TA interruption. Stable triplexes are formed at pH 6.0 at an 18-mer target site containing two TA interruptions, even though this contains eight C⁺.GC triplets. Although ^2AES and S produce stable triplexes at TA interruptions, they also interact with other base pairs, in particular, CG, although the selectivity for TA improves with increased pH. ^2AES is the best nucleoside described so far for recognition of TA within a triple-helix target.