Suicide Inhibitors of Reverse Transcriptase in the Therapy of AIDS and Other Retroviruses.

摘要

The contract period was extended to 7/31/91, without additional funding in order to complete evaluation of the antiviral activity of compounds synthesized and to evaluate the mechanism of action of certain of the synthetic analogs showing antiviral activity against HIV and other viruses in cell culture. These latter studies focused on the compound 3' uridine spiroxirane. This compound was designed as a potential suicide inhibitor of the HIV-1 transcriptase through the oxirane functionality as the 3' position. This compound showed good antiviral activity against HIV in cell culture and also against a second retrovirus (Equine Infectious Anemia Virus). In order to determine if the observed antiviral activity was due (as predicted) to inhibition of reverse transcriptase, the kinetic properties of 3' uridine spiroxirane were evaluated against the purified recombinant HIV-reverse transcriptase in vitro. In order to do this the triphosphate derivative of the nucleoside analog (the true putative inhibitor) was synthesized using a newly developed procedures for synthesizing nucleoside triphosphates.