Template. Phosphorothioate oligonucleotides duplexes as inhibitors of HIV-1 reverse transcriptase
Identifieur interne : 000381 ( France/Analysis ); précédent : 000380; suivant : 000382Template. Phosphorothioate oligonucleotides duplexes as inhibitors of HIV-1 reverse transcriptase
Auteurs : Georges Maury [France] ; Abdelaziz El Alaoui [France] ; François Morvan [France] ; Barbara Muller [Allemagne] ; Jean-Louis Imbach [France] ; Roger S. Goody [Allemagne]Source :
- Biochemical and Biophysical Research Communications [ 0006-291X ] ; 1992.
Descripteurs français
- KwdFr :
- Antiviraux (pharmacologie), Cinétique, Données de séquences moléculaires, Dénaturation d'acide nucléique, Inhibiteurs de la transcriptase inverse, Matrices (génétique), Oligodésoxyribonucléotides (pharmacologie), Polydésoxyribonucléotides (métabolisme), Protéines recombinantes (antagonistes et inhibiteurs), Séquence nucléotidique, Thermodynamique, Thionucléotides, Transcriptase inverse du VIH.
- MESH :
- antagonistes et inhibiteurs : Protéines recombinantes.
- métabolisme : Polydésoxyribonucléotides.
- pharmacologie : Antiviraux, Oligodésoxyribonucléotides.
- Pascal (Inist)
- Activité enzymatique, Activité matricielle, Cinétique, DNA polymerase RNA-dependent, Données de séquences moléculaires, Dénaturation d'acide nucléique, Inhibiteurs de la transcriptase inverse, Interaction moléculaire, Matrices (génétique), Oligonucléotide, Séquence nucléotidique, Thermodynamique, Thionucléotides, Transcriptase inverse du VIH, Virus HIV1.
English descriptors
- KwdEn :
- Antiviral Agents (pharmacology), Base Sequence, DNA polymerase RNA-dependent, Enzymatic activity, HIV Reverse Transcriptase, HIV-1 virus, Kinetics, Molecular Sequence Data, Molecular interaction, Nucleic Acid Denaturation, Oligodeoxyribonucleotides (pharmacology), Oligonucleotide, Polydeoxyribonucleotides (metabolism), Recombinant Proteins (antagonists & inhibitors), Reverse Transcriptase Inhibitors, Template activity, Templates, Genetic, Thermodynamics, Thionucleotides.
- MESH :
- chemical , antagonists & inhibitors : Recombinant Proteins.
- chemical , metabolism : Polydeoxyribonucleotides.
- chemical , pharmacology : Antiviral Agents, Oligodeoxyribonucleotides.
- Base Sequence, HIV Reverse Transcriptase, Kinetics, Molecular Sequence Data, Nucleic Acid Denaturation, Reverse Transcriptase Inhibitors, Templates, Genetic, Thermodynamics, Thionucleotides.
- Teeft :
- Academic press, Aids research, Analog, Annealed, Biophysical, Biophysical research communications, Competitive inhibition, Dissociation constants, Duplex, Duplex poly, Experimental conditions, First stage, First step, Fluorescence experiments, Fluorescence measurements, Free enzyme, High concentrations, Human retrovirus, Hybrid, Inhibitor, Inhibitor concentrations, Inhibitor properties, Inhibitory properties, Kinetic constants, Nucleotide, Oligomers, Oligonucleotides, Phosphorothioate, Phosphorothioate oligonucleotides, Poly, Primer, Primer analogs, Steady state, Substrate properties, Transcriptase, Uncompetitive inhibition.
Abstract
Summary: We have investigated the interaction between a number of 14 mers phosphorothioate oligonucleotides and HIV-1 reverse transcriptase. Two methods were used to measure the affinity of the analogs for the enzyme. In the first, the oligonucleotide or its duplex with Poly(rl) were used as inhibitors of the enzyme using Poly(rA).(dT)14 as template primer. In the second, the oligonucleotides or their duplexes were used to displace a fluorescent template.primer complex of known affinity from its binding site on reverse transcriptase. The two methods gave the same relative order of affinitiy. Phosphorothioate oligodeoxyribonucleotides had a much higher affinity than oligo(dC)14 and it was increased on hybridization. Quantitatively similar results were obtained for S(dC)14 or its analog with bases in the a-configuration. Of the analogs tested, only S(dC)14 showed priming activity.
Url:
DOI: 10.1016/S0006-291X(05)81540-2
Affiliations:
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xml:lang="en"><term>Antiviral Agents (pharmacology)</term><term>Base Sequence</term><term>DNA polymerase RNA-dependent</term><term>Enzymatic activity</term><term>HIV Reverse Transcriptase</term><term>HIV-1 virus</term><term>Kinetics</term><term>Molecular Sequence Data</term><term>Molecular interaction</term><term>Nucleic Acid Denaturation</term><term>Oligodeoxyribonucleotides (pharmacology)</term><term>Oligonucleotide</term><term>Polydeoxyribonucleotides (metabolism)</term><term>Recombinant Proteins (antagonists & inhibitors)</term><term>Reverse Transcriptase Inhibitors</term><term>Template activity</term><term>Templates, Genetic</term><term>Thermodynamics</term><term>Thionucleotides</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antiviraux (pharmacologie)</term><term>Cinétique</term><term>Données de séquences moléculaires</term><term>Dénaturation d'acide nucléique</term><term>Inhibiteurs de la transcriptase inverse</term><term>Matrices (génétique)</term><term>Oligodésoxyribonucléotides (pharmacologie)</term><term>Polydésoxyribonucléotides (métabolisme)</term><term>Protéines recombinantes (antagonistes et inhibiteurs)</term><term>Séquence nucléotidique</term><term>Thermodynamique</term><term>Thionucléotides</term><term>Transcriptase inverse du VIH</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Recombinant Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Polydeoxyribonucleotides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Oligodeoxyribonucleotides</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines recombinantes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Polydésoxyribonucléotides</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Oligodésoxyribonucléotides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Base Sequence</term><term>HIV Reverse Transcriptase</term><term>Kinetics</term><term>Molecular Sequence Data</term><term>Nucleic Acid Denaturation</term><term>Reverse Transcriptase Inhibitors</term><term>Templates, Genetic</term><term>Thermodynamics</term><term>Thionucleotides</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Activité enzymatique</term><term>Activité matricielle</term><term>Cinétique</term><term>DNA polymerase RNA-dependent</term><term>Données de séquences moléculaires</term><term>Dénaturation d'acide nucléique</term><term>Inhibiteurs de la transcriptase inverse</term><term>Interaction moléculaire</term><term>Matrices (génétique)</term><term>Oligonucléotide</term><term>Séquence nucléotidique</term><term>Thermodynamique</term><term>Thionucléotides</term><term>Transcriptase inverse du VIH</term><term>Virus HIV1</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Academic press</term><term>Aids research</term><term>Analog</term><term>Annealed</term><term>Biophysical</term><term>Biophysical research communications</term><term>Competitive inhibition</term><term>Dissociation constants</term><term>Duplex</term><term>Duplex poly</term><term>Experimental conditions</term><term>First stage</term><term>First step</term><term>Fluorescence experiments</term><term>Fluorescence measurements</term><term>Free enzyme</term><term>High concentrations</term><term>Human retrovirus</term><term>Hybrid</term><term>Inhibitor</term><term>Inhibitor concentrations</term><term>Inhibitor properties</term><term>Inhibitory properties</term><term>Kinetic constants</term><term>Nucleotide</term><term>Oligomers</term><term>Oligonucleotides</term><term>Phosphorothioate</term><term>Phosphorothioate oligonucleotides</term><term>Poly</term><term>Primer</term><term>Primer analogs</term><term>Steady state</term><term>Substrate properties</term><term>Transcriptase</term><term>Uncompetitive inhibition</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Summary: We have investigated the interaction between a number of 14 mers phosphorothioate oligonucleotides and HIV-1 reverse transcriptase. Two methods were used to measure the affinity of the analogs for the enzyme. In the first, the oligonucleotide or its duplex with Poly(rl) were used as inhibitors of the enzyme using Poly(rA).(dT)14 as template primer. In the second, the oligonucleotides or their duplexes were used to displace a fluorescent template.primer complex of known affinity from its binding site on reverse transcriptase. The two methods gave the same relative order of affinitiy. Phosphorothioate oligodeoxyribonucleotides had a much higher affinity than oligo(dC)14 and it was increased on hybridization. Quantitatively similar results were obtained for S(dC)14 or its analog with bases in the a-configuration. Of the analogs tested, only S(dC)14 showed priming activity.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>France</li></country><region><li>Languedoc-Roussillon</li><li>Occitanie (région administrative)</li></region><settlement><li>Montpellier Cédex 5</li></settlement></list><tree><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Maury, Georges" sort="Maury, Georges" uniqKey="Maury G" first="Georges" last="Maury">Georges Maury</name></region><name sortKey="Alaoui, Abdelaziz El" sort="Alaoui, Abdelaziz El" uniqKey="Alaoui A" first="Abdelaziz El" last="Alaoui">Abdelaziz El Alaoui</name><name sortKey="Imbach, Jean Louis" sort="Imbach, Jean Louis" uniqKey="Imbach J" first="Jean-Louis" last="Imbach">Jean-Louis Imbach</name><name sortKey="Morvan, Francois" sort="Morvan, Francois" uniqKey="Morvan F" first="François" last="Morvan">François Morvan</name></country><country name="Allemagne"><noRegion><name sortKey="Muller, Barbara" sort="Muller, Barbara" uniqKey="Muller B" first="Barbara" last="Muller">Barbara Muller</name></noRegion><name sortKey="Goody, Roger S" sort="Goody, Roger S" uniqKey="Goody R" first="Roger S." last="Goody">Roger S. 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