Improvement of sequence selectivity in triple helical recognition of RNA by phenylalanine-derived PNA.

Modified peptide nucleic acids (PNA) containing one or two thymine PNA monomers derived from phenylalanine were synthesized. Triple helix formation by these modified PNAs with RNA and DNA hairpins having a variable base pair in the middle of the helix were studied using isothermal titration calorimetry and compared with triple helix formation by non-modified PNAs. While unmodified PNA had low sequence selectivity against mismatched hairpins, introduction of one or two phenylalanine-derived monomers significantly increased the mismatch discrimination and sequence selectivity of the modified PNA. Consistent with our previous observations, PNA formed more stable triple helices with RNA than with DNA. Interestingly, the phenylalanine modification further improved the preference of PNA for RNA over DNA hairpin.