Extended DNA-recognition repertoire of peptide nucleic acid (PNA): PNA-dsDNA triplex formed with cytosine-rich homopyrimidine PNA.
Peptide nucleic acid (PNA) is an oligonucleotide mimic in which the backbone of DNA has been replaced by a pseudopeptide.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.
Wittung
P
P
Department of Physical Chemistry, Chalmers University of Technology, S-41296 Gothenburg, Sweden.
Nielsen
P
P
Nordén
B
B
D002942:Circular Dichroism; D003596:Cytosine / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011687:Purines / Q000737:chemistry / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism*
D009841:Oligonucleotides; D010455:Peptides; D011687:Purines; D011743:Pyrimidines; D003596:Cytosine; D004247:DNA