Comparative hybrid arrest by tandem antisense oligodeoxyribonucleotides or oligodeoxyribonucleoside methylphosphonates in a cell-free system.
Identifieur interne : 001994 ( Ncbi/Checkpoint ); précédent : 001993; suivant : 001995Comparative hybrid arrest by tandem antisense oligodeoxyribonucleotides or oligodeoxyribonucleoside methylphosphonates in a cell-free system.
Auteurs : L J Maher ; B J DolnickSource :
- Nucleic acids research [ 0305-1048 ] ; 1988.
Descripteurs français
- KwdFr :
- ARN messager (), ARN messager (métabolisme), Animaux, Biosynthèse des protéines (), Dihydrofolate reductase (biosynthèse), Dihydrofolate reductase (génétique), Dépression chimique, Désoxyribonucléotides (métabolisme), Désoxyribonucléotides (pharmacologie), Désoxyribonucléotides (synthèse chimique), Endoribonucleases (métabolisme), Humains, Lapins, Oligodésoxyribonucléotides (métabolisme), Oligodésoxyribonucléotides (pharmacologie), Oligodésoxyribonucléotides (synthèse chimique), Ribonuclease H, Synergie des médicaments, Système acellulaire.
- MESH :
- biosynthèse : Dihydrofolate reductase.
- génétique : Dihydrofolate reductase.
- métabolisme : ARN messager, Désoxyribonucléotides, Endoribonucleases, Oligodésoxyribonucléotides.
- pharmacologie : Désoxyribonucléotides, Oligodésoxyribonucléotides.
- synthèse chimique : Désoxyribonucléotides, Oligodésoxyribonucléotides.
- ARN messager, Animaux, Biosynthèse des protéines, Dépression chimique, Humains, Lapins, Ribonuclease H, Synergie des médicaments, Système acellulaire.
English descriptors
- KwdEn :
- Animals, Cell-Free System, Deoxyribonucleotides (chemical synthesis), Deoxyribonucleotides (metabolism), Deoxyribonucleotides (pharmacology), Depression, Chemical, Drug Synergism, Endoribonucleases (metabolism), Humans, Oligodeoxyribonucleotides (chemical synthesis), Oligodeoxyribonucleotides (metabolism), Oligodeoxyribonucleotides (pharmacology), Protein Biosynthesis (drug effects), RNA, Messenger (drug effects), RNA, Messenger (metabolism), Rabbits, Ribonuclease H, Tetrahydrofolate Dehydrogenase (biosynthesis), Tetrahydrofolate Dehydrogenase (genetics).
- MESH :
- chemical , biosynthesis : Tetrahydrofolate Dehydrogenase.
- chemical , chemical synthesis : Deoxyribonucleotides, Oligodeoxyribonucleotides.
- chemical , drug effects : RNA, Messenger.
- chemical , genetics : Tetrahydrofolate Dehydrogenase.
- chemical , metabolism : Deoxyribonucleotides, Endoribonucleases, Oligodeoxyribonucleotides, RNA, Messenger.
- chemical , pharmacology : Deoxyribonucleotides, Oligodeoxyribonucleotides.
- drug effects : Protein Biosynthesis.
- Animals, Cell-Free System, Depression, Chemical, Drug Synergism, Humans, Rabbits, Ribonuclease H.
Abstract
Antisense oligonucleotides containing either anionic diester or neutral methylphosphonate internucleoside linkages were prepared by automated synthesis, and were compared for their ability to arrest translation of human dihydrofolate reductase (DHFR) mRNA in a nuclease treated rabbit reticulocyte lysate. In the case of oligodeoxyribonucleotides, tandem targeting of three 14-mers resulted in synergistic and complete selective inhibition of DHFR synthesis at a total oligomer concentration of 25 microM. Hybrid arrest by three or six tandem oligodeoxyribonucleoside methylphosphonates was dramatically less effective. This difference does not result from preferential recognition of hybrids involving oligodeoxyribonucleotides by endogenous RNaseH activity. A ribonuclease protection assay demonstrated that antisense oligodeoxyribonucleoside methylphosphonates bind selectively to target RNA sequences, but with 275 fold lower affinity than the corresponding oligodeoxyribonucleotides. This low binding affinity results in poor arrest of translation, and may be related to the stereochemistry of the methylphosphonate linkage.
DOI: 10.1093/nar/16.8.3341
PubMed: 2836793
Affiliations:
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code="subField">Madison</wicri:noCountry></affiliation></author><author><name sortKey="Dolnick, B J" sort="Dolnick, B J" uniqKey="Dolnick B" first="B J" last="Dolnick">B J Dolnick</name></author></analytic><series><title level="j">Nucleic acids research</title><idno type="ISSN">0305-1048</idno><imprint><date when="1988" type="published">1988</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell-Free System</term><term>Deoxyribonucleotides (chemical synthesis)</term><term>Deoxyribonucleotides (metabolism)</term><term>Deoxyribonucleotides (pharmacology)</term><term>Depression, Chemical</term><term>Drug Synergism</term><term>Endoribonucleases (metabolism)</term><term>Humans</term><term>Oligodeoxyribonucleotides (chemical synthesis)</term><term>Oligodeoxyribonucleotides (metabolism)</term><term>Oligodeoxyribonucleotides (pharmacology)</term><term>Protein Biosynthesis (drug 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H</term><term>Synergie des médicaments</term><term>Système acellulaire</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Tetrahydrofolate Dehydrogenase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Deoxyribonucleotides</term><term>Oligodeoxyribonucleotides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>RNA, Messenger</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Tetrahydrofolate Dehydrogenase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Deoxyribonucleotides</term><term>Endoribonucleases</term><term>Oligodeoxyribonucleotides</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Deoxyribonucleotides</term><term>Oligodeoxyribonucleotides</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Dihydrofolate reductase</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Protein Biosynthesis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Dihydrofolate reductase</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN messager</term><term>Désoxyribonucléotides</term><term>Endoribonucleases</term><term>Oligodésoxyribonucléotides</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Désoxyribonucléotides</term><term>Oligodésoxyribonucléotides</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Désoxyribonucléotides</term><term>Oligodésoxyribonucléotides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell-Free System</term><term>Depression, Chemical</term><term>Drug Synergism</term><term>Humans</term><term>Rabbits</term><term>Ribonuclease H</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ARN messager</term><term>Animaux</term><term>Biosynthèse des protéines</term><term>Dépression chimique</term><term>Humains</term><term>Lapins</term><term>Ribonuclease H</term><term>Synergie des médicaments</term><term>Système acellulaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Antisense oligonucleotides containing either anionic diester or neutral methylphosphonate internucleoside linkages were prepared by automated synthesis, and were compared for their ability to arrest translation of human dihydrofolate reductase (DHFR) mRNA in a nuclease treated rabbit reticulocyte lysate. In the case of oligodeoxyribonucleotides, tandem targeting of three 14-mers resulted in synergistic and complete selective inhibition of DHFR synthesis at a total oligomer concentration of 25 microM. Hybrid arrest by three or six tandem oligodeoxyribonucleoside methylphosphonates was dramatically less effective. This difference does not result from preferential recognition of hybrids involving oligodeoxyribonucleotides by endogenous RNaseH activity. A ribonuclease protection assay demonstrated that antisense oligodeoxyribonucleoside methylphosphonates bind selectively to target RNA sequences, but with 275 fold lower affinity than the corresponding oligodeoxyribonucleotides. This low binding affinity results in poor arrest of translation, and may be related to the stereochemistry of the methylphosphonate linkage.</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Dolnick, B J" sort="Dolnick, B J" uniqKey="Dolnick B" first="B J" last="Dolnick">B J Dolnick</name><name sortKey="Maher, L J" sort="Maher, L J" uniqKey="Maher L" first="L J" last="Maher">L J Maher</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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