title: Inhibition of multi-drug resistant HIV-1 reverse transcriptase by nucleoside β-triphosphates.
abstract: Despite the success of potent reverse transcriptase (RT) inhibitors against human immunodeficiency virus type 1 (HIV-1) in combination regimens, the development of drug resistant RTs constitutes a major hurdle for the long-term efficacy of current antiretroviral therapy. Nucleoside β-triphosphate analogs of adenosine and nucleoside reverse transcriptase inhibitors (NRTIs) (3'-azido-2',3'-dideoxythymidine (AZT), 3'-fluoro-2',3'-dideoxythymidine (FLT), and 2',3'-didehydro-2',3'-dideoxythymidine (d4T)) were synthesized and their inhibitory activities were evaluated against wild-type and multidrug resistant HIV-1 RTs. Adenosine β-triphosphate (1) and AZT β-triphosphate (2) completely inhibited the DNA polymerase activity of wild type, the NRTI multi resistant, and nonnucleoside RT inhibitors (NNRTI) resistant HIV-1 RT at 10nM, 10 and 100 μM, respectively.
authors: Center for AIDS Health Disparities Research, Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.
authors: Chandravanu
authors: C
authors: Dash
authors: Yousef
authors: Y
authors: Ahmadibeni
authors: Michael J
authors: MJ
authors: Hanley
authors: Jui
authors: J
authors: Pandhare
authors: Mathias
authors: M
authors: Gotte
authors: Stuart F J
authors: SF
authors: Le Grice
authors: Keykavous
authors: K
authors: Parang
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