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Peptide nucleic acid (PNA) is an oligonucleotide mimic in which the ba ckbone of DNA has been replaced by a pseudopeptide.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