Antisense properties of duplex- and triplex-forming PNAs.
The potential of peptide nucleic acids (PNAs) as specific inhibitors of translation has been studied. PNAs with a mixed purine/pyrimidine sequence form duplexes, while homopyrimidine PNAs form (PNA)2/RNA triplexes with complementary sequences on RNA. We show here that neither of these PNA/RNA structures are substrates for RNase H. Translation experiments in cell-free extracts showed that a 15mer duplex-forming PNA blocked translation in a dose-dependent manner when the target was 5'-proximal to the AUG start codon on the RNA, whereas similar 10-, 15- or 20mer PNAs had no effect when targeted towards sequences in the coding region. Triplex-forming 10mer PNAs were efficient and specific antisense agents with a target overlapping the AUG start codon and caused arrest of ribosome elongation with a target positioned in the coding region of the mRNA. Furthermore, translation could be blocked with a 6mer bisPNA or with a clamp PNA, forming partly a triplex, partly a duplex, with its target sequence in the coding region of the mRNA.
Knudsen
H
H
Center for Biomolecular Recognition, Department of Biochemistry and Genetics, The Panum Institute, Copenhagen, Denmark.
Nielsen
P E
PE
D001483:Base Sequence; D008969:Molecular Sequence Data; D009696:Nucleic Acids / Q000138:chemical synthesis / Q000235:genetics* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000378:metabolism*
D009696:Nucleic Acids; D016376:Oligonucleotides, Antisense; D010455:Peptides; D012313:RNA