BisPNA targeting to DNA: effect of neutral loop on DNA duplex strand invasion by aepPNA-N7G/aepPNA-C substituted peptide nucleic acids

Abstract

N7-Alkyl-substituted guanine (N7G) as a CH⁺ mimic has been introduced into aminoethylglycyl PNA (aegPNA) forming a hairpin through a neutral linker derived from bis(tetraethylene) glycol (teg-teg). These form pH-independent PNA₂:DNA triplexes with complementary DNA sequences. The introduction of chiral, cationic aminoethylprolyl (aep) units with C and the CH⁺ mimic N7G in the backbone of the hairpin bisPNAs with a neutral teg-teg linker, influenced the recognition of complementary DNA in an orientation-selective manner. Fluorescence assay was used to examine the process of strand invasion of the target DNA duplex by the modified hairpin bisPNAs with the neutral teg linker and comparison of results of previous studies employing cationic linkers suggested the triplex formation to be a two-step process, with the preferred formation of HG bonds in the first step.