Peptide nucleic acid (PNA) is an oligonucleotide mimic in which the ba
ckbone of DNA has been replaced by a pseudopeptide. We here show that
there are distinct variations as to how PNA oligomers interact with do
uble-stranded DNA depending on choice of nucleobases. Thymine-rich hom
opyrimidine PNA oligomers recognise double-stranded polynucleotides by
forming PNA(2)-DNA triplexes with the DNA purine strand. By contrast,
cytosine-rich homopyrimidine PNAs add to double-stranded polynucleoti
des as Hoogsteen strands, forming PNA-DNA(2) triplexes, while homopuri
ne, or alternating thymine-guanine, PNA oligomers invade DNA to form P
NA-DNA duplexes.