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.