Extended DNA-Recognition Repertoire of Peptide Nucleic Acid (PNA): PNA−dsDNA Triplex Formed with Cytosine-Rich Homopyrimidine PNA

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Abstract
Peptide nucleic acid (PNA) is an oligonucleotide mimic in which the backbone of DNA has been replaced by a pseudopeptide. Thymine-rich homopyrimidine PNA oligomers have been found to recognize double-stranded DNA targets by displacement of the pyrimidine DNA strand and forming an internal Watson−Crick−Hoogsteen base-paired PNA(pyr)−DNA(pu)−PNA(pyr) triplex. We here show that cytosine-rich homopyrimidine PNA sequences instead add to double-stranded polynucleotide targets as Hoogsteen strands forming PNA(pyr)−DNA(pu)−DNA(pyr) triplexes. Furthermore, PNA strands with homopurine or alternating thymine-guanine sequences are shown to invade their respective DNA targets by displacing the identical DNA strands of the polynucleotides and forming new PNA−DNA duplexes. These results indicate distinct mechanistic variations as to how PNA interacts with a DNA target depending on choice of nucleobases, which could be of importance for future design of gene-specific diagnostic or therapeutic agents.