Template. Phosphorothioate oligonucleotides duplexes as inhibitors of HIV-1 reverse transcriptase
Identifieur interne : 000254 ( Istex/Curation ); précédent : 000253; suivant : 000255Template. 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.
English descriptors
- 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
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<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>
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