Investigation of the stereochemical course of DNA synthesis catalysed by human immunodeficiency virus type 1 reverse transcriptase.
The Sp-isomer of thymidine 5'-O-(1-thiotriphosphate) is used as substrate by HIV-1 reverse transcriptase. The absolute configuration of the internucleotide linkage in the oligonucleotide product was identified by 31p NMR spectroscopy to be the Rp-isomer, indicating that incorporation of dTTP alpha S into the oligonucleotide proceeded with inversion of configuration at the alpha-phosphorus. The mechanistic implications of these observations are discussed.
Hopkins
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Division of Virology, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
Furman
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Painter
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D002384:Catalysis; D004247:DNA / Q000096:biosynthesis* / Q000648:ultrastructure; D006678:HIV / Q000201:enzymology*; D066298:In Vitro Techniques; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors; D013237:Stereoisomerism
D018894:Reverse Transcriptase Inhibitors; D004247:DNA; D012194:RNA-Directed DNA Polymerase