2--3--dideoxyguanosine-5--triphosphate has been researched along with thymidine-5--triphosphate* in 2 studies
2 other study(ies) available for 2--3--dideoxyguanosine-5--triphosphate and thymidine-5--triphosphate
| Article | Year |
|---|---|
Analysis of HIV-2 RT mutants provides evidence that resistance of HIV-1 RT and HIV-2 RT to nucleoside analogs involves a repositioning of the template-primer.
Mutations that confer resistance to nucleoside analogs do not cluster around the deoxynucleotide triphosphate (dNTP) binding site. Instead, these mutations appear to lie along the groove in the enzyme where the template-primer binds. Based on such structural data and on complementary biochemical analyses, it has been suggested that resistance to nucleoside analogs involves repositioning of the template-primer. We have prepared mutations in HIV-2 RT that are the homologs of mutations that confer resistance to nucleoside analogs in HIV-1 RT. Analysis of the behavior of HIV-2 RT mutants (Leu74Val, Glu89Gly, Ser215Tyr, Leu74Val/Ser215Tyr and Glu89Gly/Ser215Tyr) in vitro confirms the results obtained with HIV-1 RT: resistance is a function of the length of the template overhang. These analyses also suggest that the homolog in HIV-2 RT of one of the mutations that confers resistance to AZT in HIV-1 RT (Thr215Tyr) confers resistance by repositioning of the template-primer. Topics: Deoxyguanine Nucleotides; Deoxyribonucleotides; Dideoxynucleotides; DNA Primers; DNA, Viral; Drug Resistance, Microbial; HIV Reverse Transcriptase; HIV-1; HIV-2; Humans; Models, Molecular; Mutation; Recombinant Proteins; Reverse Transcriptase Inhibitors; RNA-Directed DNA Polymerase; Templates, Genetic; Thymine Nucleotides | 1997 |
Mechanism of inhibition of human immunodeficiency virus type 1 reverse transcriptase and human DNA polymerases alpha, beta, and gamma by the 5'-triphosphates of carbovir, 3'-azido-3'-deoxythymidine, 2',3'-dideoxyguanosine and 3'-deoxythymidine. A novel RN
Carbovir (the carbocyclic analog of 2'-3'-didehydro-2',3'-dideoxyguanosine) is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) replication. Assays were developed to assess the mechanism of inhibition by the 5'-triphosphate of carbovir of HIV-1 reverse transcriptase using either RNA or DNA templates that contain all four natural nucleotides. Carbovir-TP was a potent inhibitor of HIV-1 reverse transcriptase using either template with Ki values similar to that observed by AZT-TP, ddGTP, and ddTTP. The kinetic constants for incorporation of these nucleotide analogs into DNA by HIV-1 reverse transcriptase using either template were similar to the values seen for their respective natural nucleotides. In addition, the incorporation of either carbovir-TP or AZT-TP in the presence of dGTP or dTTP, respectively, indicated that the mechanism of inhibition by these two nucleotide analogs was due to their incorporation into the DNA resulting in chain termination. Carbovir-TP was not a potent inhibitor of DNA polymerase alpha, beta, or gamma, or DNA primase. Given the potent activity of carbovir-TP against HIV-1 reverse transcriptase and its lack of activity against human DNA polymerases, we believe that further evaluation of this compound as a potential drug for the treatment of HIV-1 infection is warranted. Topics: Antiviral Agents; Base Sequence; Deoxyguanine Nucleotides; Dideoxynucleotides; DNA; DNA Polymerase I; DNA Polymerase II; DNA Polymerase III; HIV-1; Humans; In Vitro Techniques; Kinetics; Molecular Sequence Data; Reverse Transcriptase Inhibitors; RNA; Templates, Genetic; Thymine Nucleotides; Zidovudine | 1991 |