2-aminopurine-dioxolane and Acquired-Immunodeficiency-Syndrome

2-aminopurine-dioxolane has been researched along with Acquired-Immunodeficiency-Syndrome* in 2 studies

Other Studies

2 other study(ies) available for 2-aminopurine-dioxolane and Acquired-Immunodeficiency-Syndrome

Article	Year
Dioxolane guanosine 5'-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase. Steady state and pre-steady state kinetic analyses. The Journal of biological chemistry, 2003, May-23, Volume: 278, Issue:21 The frequency of human immunodeficiency virus, type 1 (HIV-1) mutations in response to antiviral therapy and resulting drug resistance is of major concern. Amdoxovir ((-)-beta-D-2,6-diaminopurine dioxolane), the prodrug of dioxolane guanosine (DXG), is currently in phase I/II clinical development for the treatment of HIV-1 infection. In vitro, HIV-1 mutants resistant to 3'-azido-3'-deoxythymidine (M41L/D67N/K70R/T215Y/K219Q) and (-)beta-L-2',3'-dideoxy-3'-thiacytidine (3TC) (M184V) remain sensitive to DXG. HIV-1 with the reverse transcriptase mutations K65R, L74V, and/or Q151M were less sensitive to DXG, whereas the mutation K103N re-sensitized the virus to the inhibitory effect of DXG. In order to understand these observations at the enzyme level, we investigated the inhibition of the HIV-1 reverse transcriptase-catalyzed viral DNA synthesis by dioxolane guanosine 5'-triphosphate (DXG-TP), 3'-azido-3'-deoxythymidine-TP, and 3TC-TP by using steady state kinetic analysis and the incorporation of DXG-5'-monophosphate by using pre-steady state kinetic analysis. This mechanistic study provided detailed information on the amdoxovir-related drug resistance at a molecular level. Overall, the enzymatic data correlated well with the antiviral data obtained from cell culture experiments and further supported the use of amdoxovir for the treatment of nucleoside reverse transcriptase inhibitor-experienced patients. Topics: Acquired Immunodeficiency Syndrome; Cytidine Triphosphate; Deoxycytidine Monophosphate; Deoxyguanine Nucleotides; Dideoxynucleotides; Dioxolanes; DNA, Viral; Drug Resistance, Viral; Guanosine; Guanosine Triphosphate; HIV Reverse Transcriptase; HIV-1; Lamivudine; Mutation; Reverse Transcriptase Inhibitors; Substrate Specificity; Thymidine Monophosphate; Thymine Nucleotides; Zidovudine	2003
New antiretroviral agents. The Hopkins HIV report : a bimonthly newsletter for healthcare providers, 2001, Volume: 13, Issue:2 Topics: Acquired Immunodeficiency Syndrome; Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Carbamates; Deoxycytidine; Dioxolanes; Drugs, Investigational; Emtricitabine; Furans; Guanosine; HIV Fusion Inhibitors; Humans; Imidazoles; Oligopeptides; Organophosphates; Organophosphonates; Organophosphorus Compounds; Prodrugs; Protease Inhibitors; Pyridines; Pyrones; Quinazolines; Reverse Transcriptase Inhibitors; Sulfonamides; Sulfur Compounds; Tenofovir	2001

Article

Year

Dioxolane guanosine 5'-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase. Steady state and pre-steady state kinetic analyses.

The Journal of biological chemistry, 2003, May-23, Volume: 278, Issue:21

The frequency of human immunodeficiency virus, type 1 (HIV-1) mutations in response to antiviral therapy and resulting drug resistance is of major concern. Amdoxovir ((-)-beta-D-2,6-diaminopurine dioxolane), the prodrug of dioxolane guanosine (DXG), is currently in phase I/II clinical development for the treatment of HIV-1 infection. In vitro, HIV-1 mutants resistant to 3'-azido-3'-deoxythymidine (M41L/D67N/K70R/T215Y/K219Q) and (-)beta-L-2',3'-dideoxy-3'-thiacytidine (3TC) (M184V) remain sensitive to DXG. HIV-1 with the reverse transcriptase mutations K65R, L74V, and/or Q151M were less sensitive to DXG, whereas the mutation K103N re-sensitized the virus to the inhibitory effect of DXG. In order to understand these observations at the enzyme level, we investigated the inhibition of the HIV-1 reverse transcriptase-catalyzed viral DNA synthesis by dioxolane guanosine 5'-triphosphate (DXG-TP), 3'-azido-3'-deoxythymidine-TP, and 3TC-TP by using steady state kinetic analysis and the incorporation of DXG-5'-monophosphate by using pre-steady state kinetic analysis. This mechanistic study provided detailed information on the amdoxovir-related drug resistance at a molecular level. Overall, the enzymatic data correlated well with the antiviral data obtained from cell culture experiments and further supported the use of amdoxovir for the treatment of nucleoside reverse transcriptase inhibitor-experienced patients.

Topics: Acquired Immunodeficiency Syndrome; Cytidine Triphosphate; Deoxycytidine Monophosphate; Deoxyguanine Nucleotides; Dideoxynucleotides; Dioxolanes; DNA, Viral; Drug Resistance, Viral; Guanosine; Guanosine Triphosphate; HIV Reverse Transcriptase; HIV-1; Lamivudine; Mutation; Reverse Transcriptase Inhibitors; Substrate Specificity; Thymidine Monophosphate; Thymine Nucleotides; Zidovudine

2003

New antiretroviral agents.

The Hopkins HIV report : a bimonthly newsletter for healthcare providers, 2001, Volume: 13, Issue:2

Topics: Acquired Immunodeficiency Syndrome; Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Carbamates; Deoxycytidine; Dioxolanes; Drugs, Investigational; Emtricitabine; Furans; Guanosine; HIV Fusion Inhibitors; Humans; Imidazoles; Oligopeptides; Organophosphates; Organophosphonates; Organophosphorus Compounds; Prodrugs; Protease Inhibitors; Pyridines; Pyrones; Quinazolines; Reverse Transcriptase Inhibitors; Sulfonamides; Sulfur Compounds; Tenofovir

2001