Abstract
We have compared the HIV-1 RT mutants containing the single substitutions L100I, K103N, V106A, V179D, Y181I and Y188L, known to confer NNI-resistance in treated patients, to HIV-1 RT wt for their sensitivity towards inhibition by D- and L-deoxy- and dideoxy-nucleoside tiphosphates. The results showed a differential effect of the substitutions on the affinity for both D- and L-enantiomers of deoxy- and dideoxy-nucleoside triphosphates and provide a rationale for the utilization of L-dideoxynucleoside analogs with NNI in combination chemotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-HIV Agents / administration & dosage
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Anti-HIV Agents / metabolism*
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Anti-HIV Agents / therapeutic use
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Binding Sites
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Dideoxynucleosides / administration & dosage
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Dideoxynucleosides / therapeutic use
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Drug Therapy, Combination
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HIV Infections / drug therapy*
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HIV Reverse Transcriptase / chemistry
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HIV Reverse Transcriptase / genetics
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HIV Reverse Transcriptase / metabolism*
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Humans
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Kinetics
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Mutation
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Protein Structure, Secondary
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Pyrimidine Nucleotides / administration & dosage
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Pyrimidine Nucleotides / metabolism*
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Pyrimidine Nucleotides / therapeutic use
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Reverse Transcriptase Inhibitors / administration & dosage
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Reverse Transcriptase Inhibitors / metabolism*
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Reverse Transcriptase Inhibitors / therapeutic use
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Stereoisomerism
Substances
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Anti-HIV Agents
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Dideoxynucleosides
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Pyrimidine Nucleotides
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Reverse Transcriptase Inhibitors
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HIV Reverse Transcriptase