Abstract
To investigate the biochemical basis of the HIV-1 resistance to AZT we obtained the RT mutant containing four amino acid substitutions by an oligonucleotide-directed mutagenesis technique. Enzymatic properties of the wild type and mutant RTs were compared. 'AZT-resistant' mutations in RT were shown to be associated with the reduced capability of AZT-TP to block the DNA- but not RNA-directed DNA synthesis.
MeSH terms
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Antiviral Agents / pharmacology*
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DNA, Viral / biosynthesis
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Dideoxynucleotides
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Drug Resistance, Microbial / genetics
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HIV Reverse Transcriptase
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HIV-1 / drug effects
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HIV-1 / enzymology*
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Mutagenesis, Site-Directed
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RNA-Directed DNA Polymerase / genetics*
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RNA-Directed DNA Polymerase / metabolism
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Recombinant Proteins / metabolism
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Reverse Transcriptase Inhibitors
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Substrate Specificity
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Thymine Nucleotides / pharmacology*
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Zidovudine / analogs & derivatives*
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Zidovudine / pharmacology
Substances
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Antiviral Agents
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DNA, Viral
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Dideoxynucleotides
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Recombinant Proteins
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Reverse Transcriptase Inhibitors
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Thymine Nucleotides
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Zidovudine
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zidovudine triphosphate
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HIV Reverse Transcriptase
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RNA-Directed DNA Polymerase