Shape selective bifacial recognition of double helical DNA

An impressive array of antigene approaches has been developed for recognition of double helical DNA over the past three decades; however, few have exploited the ‘Watson–Crick’ base-pairing rules for establishing sequence-specific recognition. One approach employs peptide nucleic acid as a molecular reagent and strand invasion as a binding mode. However, even with integration of the latest conformationally-preorganized backbone design, such an approach is generally confined to sub-physiological conditions due to the lack of binding energy. Here we report the use of a class of shape-selective, bifacial nucleic acid recognition elements, namely Janus bases, for targeting double helical DNA or RNA. Binding occurs in a highly sequence-specific manner under physiologically relevant conditions. The work may provide a foundation for the design of oligonucleotides for targeting the secondary and tertiary structures of nucleic acid biopolymers. Peptide nucleic acids (PNAs) can invade canonical nucleic acid dimers but may be limited to certain sequences or perform poorly under physiological conditions. Here PNAs containing Janus bases invade a range of RNA and DNA sequences via Watson-Crick base pairing under near-physiological conditions.