title: Human immunodeficiency virus reverse transcriptase. General properties and its interactions with nucleoside triphosphate analogs.
abstract: Using affinity purified human immunodeficiency virus (HIV) reverse transcriptase the reaction assay conditions were determined. The optimum incorporation of dTMP into the (rA)n(dT)10 template with HIV reverse transcriptase required 6 mM MgCl2 and 80 mM KCl. The template specificity of HIV reverse transcriptase is quite different from those of the human gamma-polymerase-associated reverse transcriptase or avian virus reverse transcriptase. The preferential inhibition of HIV reverse transcriptase as compared to human gamma-reverse transcriptase was observed with several nucleoside analog triphosphates. The Ki values for thymidine triphosphate analogs with HIV reverse transcriptase ranged from 5 to 13 nM with decreasing effectiveness for 3'-fluoro greater than 3'-amino greater than 2',3'-dideoxy greater than 3'-azido groups. This study provides information on the structure activity relationships of the triphosphate analogs inhibitory effects on HIV reverse transcriptase versus human gamma-polymerase-associated reverse transcriptase, and the possible mechanisms of action of 3' azido thymidine and the 2',3'-dideoxynucleosides, and also identifies other nucleoside analogs for possible development as inhibitors of HIV.
mesh_terms: D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D006678:HIV / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D009711:Nucleotides / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013942:Thymine Nucleotides / Q000378:metabolism
chemical_list: D003848:Deoxyguanine Nucleotides; D009711:Nucleotides; D013942:Thymine Nucleotides; C029603:deoxyguanosine triphosphate; D012194:RNA-Directed DNA Polymerase; C024157:thymidine 5'-triphosphate