Antisense properties of duplex- and triplex-forming PNAs

Nucleic Acids Res. 1996 Feb 1;24(3):494-500. doi: 10.1093/nar/24.3.494.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Molecular Sequence Data
  • Nucleic Acids / chemical synthesis
  • Nucleic Acids / genetics*
  • Nucleic Acids / metabolism
  • Oligonucleotides, Antisense / chemical synthesis
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism*
  • Peptides / chemical synthesis
  • Peptides / genetics*
  • Peptides / metabolism
  • RNA / metabolism*

Substances

  • Nucleic Acids
  • Oligonucleotides, Antisense
  • Peptides
  • RNA