PMID: 8602363Feb 1, 1996Paper

Antisense properties of duplex- and triplex-forming PNAs

Nucleic Acids Research
H Knudsen, P E Nielsen

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.

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Citations

Jul 7, 2009·Applied Microbiology and Biotechnology·Masashi HatamotoHiroyuki Imachi
Feb 6, 2010·Applied Microbiology and Biotechnology·Masashi HatamotoHiroyuki Imachi
Jul 5, 2002·Journal of Molecular Biology·Nathalie DiasTula Ester Saison-Behmoaras
Jan 27, 2000·Journal of Biochemical and Biophysical Methods·K Jansen, E Richelson
May 12, 2000·Biochimica Et Biophysica Acta·H J LarsenP E Nielsen
Nov 10, 2000·Advanced Drug Delivery Reviews·D A Dean
Feb 5, 2003·Advanced Drug Delivery Reviews·Uffe Koppelhus, Peter E Nielsen
Mar 14, 2000·Bioorganic & Medicinal Chemistry Letters·I KumagaiH Mihara
May 17, 2001·Bioorganic & Medicinal Chemistry Letters·I KumagaiH Mihara
Jan 1, 1999·Bioorganic & Medicinal Chemistry Letters·A C van der LaanJ H van Boom
Jan 9, 1999·Bioorganic & Medicinal Chemistry·A H KrotzP E Nielsen
Apr 29, 1999·Bioorganic & Medicinal Chemistry·J C VerheijenP F Torrence
May 5, 2001·Biomolecular Engineering·M PoogaU Langel
Apr 29, 1998·Nature Biotechnology·L Good, P E Nielsen
Dec 1, 1996·Nature Biotechnology·P M Lansdorp
Feb 1, 1997·Nature Structural Biology·H RasmussenP E Nielsen
Apr 30, 2004·Cell Research·Gan Wang, Xiaoxin S Xu
Oct 26, 2005·Chemical Communications : Chem Comm·Yamuna Krishnan-GhoshShankar Balasubramanian
May 31, 2011·Nucleosides, Nucleotides & Nucleic Acids·David W DoddRobert E Hudson
Jun 21, 2002·Antisense & Nucleic Acid Drug Development·Uffe KoppelhusPeter Eigil Nielsen
Apr 24, 2004·Oligonucleotides·Lingamanaidu V RavichandranEric G Marcusson
Aug 1, 1997·Antisense & Nucleic Acid Drug Development·C ColombierM Leng
Aug 1, 1997·Antisense & Nucleic Acid Drug Development·C Giovannangeli, C Hélène
Aug 1, 1997·Antisense & Nucleic Acid Drug Development·L Good, P E Nielsen
Jun 13, 2006·Oligonucleotides·S Bøe, E Hovig
Apr 6, 2006·Oligonucleotides·Frank Winther RasmussenUffe Koppelhus
Feb 15, 1997·Nucleic Acids Research·O HeidenreichM Nerenberg
May 21, 1998·Nucleic Acids Research·L ChristensenP E Nielsen
Jun 6, 1998·Nucleic Acids Research·L MologniC Gambacorti-Passerini
Jan 11, 2000·Nucleic Acids Research·E Grabczyk, K Usdin

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