Towards the Sequence-Selective Recognition of Double-Stranded DNA Containing Pyrimidine-Purine Interruptions by Triplex-Forming Oligonucleotides

Triplex formation with double-stranded DNA (dsDNA) by oligonucleotides has potential for applications in attractive technologies such as gene therapy and genetic diagnosis. However, triplex-forming oligonucleotides (TFOs) can only recognize homopurine strands in homopurine-homopyrimidine regions in dsDNA, either through Hoogsteen or through reverse-Hoogsteen hydrogen bonds. A straightforward and powerful approach to overcoming this sequence limitation is the development of artificial nucleic acids capable of recognizing specific pyrimidine-purine interruptions (i.e., a CG or TA base pair) in triplex formation. This review describes artificial nucleic acids, especially those containing non-natural nucleobases, developed to recognize CG or TA base pairs in dsDNA targets.