A Short Phosphodiester Window Is Sufficient to Direct RNase H-Dependent RNA Cleavage by Antisense Peptide Nucleic Acid
| Autor: | Bernard Lebleu, Ian Robbins, Sander Van Der Laan, Jeroen C. Verheijen, Charlotte Malchére, Jacques Van Boom, Lionel Bastide |
|---|---|
| Přispěvatelé: | Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Max-Planck-Institut für Plasmaphysik [Garching] (IPP), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) |
| Rok vydání: | 2000 |
| Předmět: |
Peptide Nucleic Acids
Polymers RNase P Ribonuclease H Oligonucleotides Biology Cleavage (embryo) 01 natural sciences Catalysis 03 medical and health sciences chemistry.chemical_compound Escherichia coli Genetics Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RNA Messenger RNase H 030304 developmental biology Pharmacology Drug Escherichia coli/enzymology Gene Targeting Oligonucleotides/*pharmacology Oligonucleotides 0303 health sciences Cell-Free System Dose-Response Relationship Drug Peptide nucleic acid 010405 organic chemistry musculoskeletal neural and ocular physiology Animals Catalysis Cell-Free System DNA/chemistry Dose-Response Relationship RNA DNA Oligonucleotides Antisense Messenger/drug effects/*metabolism Rabbits Ribonuclease H/drug effects/genetics/*metabolism 0104 chemical sciences chemistry Biochemistry Antisense/chemistry/*pharmacology Peptide Nucleic Acids/chemistry/*pharmacology Polymers/pharmacology Protein Biosynthesis/drug effects RNA Protein Biosynthesis Gene Targeting biological sciences Phosphodiester bond cardiovascular system biology.protein Rabbits RNA Cleavage tissues |
| Zdroj: | Antisense and Nucleic Acid Drug Development Antisense and Nucleic Acid Drug Development, Mary Ann Liebert, 2000, 10 (6), pp.463--8. ⟨10.1089/oli.1.2000.10.463⟩ |
| ISSN: | 1087-2906 |
| DOI: | 10.1089/oli.1.2000.10.463 |
| Popis: | The potential pharmacologic benefits of using peptide nucleic acid (PNA) as an antisense agent are tempered by its incapacity to activate RNase H. The mixed backbone oligonucleotide (ON) (or gapmer) approach, in which a short internal window of RNAse H-competent residues is embedded within an RNase H-incompetent ON has not been applied previously to PNA because PNA and DNA hybridize to RNA with very different helical structures, creating structural perturbations at the two PNA-DNA junctions. It is demonstrated here for the first time that a short internal phosphodiester window within a PNA is sufficient to evoke the RNase H-dependent cleavage of a targeted RNA and to abrogate translation elongation in a well-characterized in vitro assay. |
| Databáze: | OpenAIRE |
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