Comparison of the effect of Carbovir, AZT, and dideoxynucleoside triphosphates on the activity of human immunodeficiency virus reverse transcriptase and selected human polymerases.

Academic Article

Abstract

  • Carbocylic 2',3'-didehydro-2',3'-dideoxyguanosine (Carbovir; NSC 614846) is an antiretroviral agent which may be useful in the treatment of AIDS. We have synthesized the 5'-triphosphate of Carbovir and examined its ability to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (EC 2.7.7.49) and other retroviral reverse transcriptases, as well as human DNA polymerases alpha, beta, gamma (EC 2.7.7.7) and DNA primase (EC 2.7.7.6). Carbovir triphosphate emerges as a highly selective inhibitor of reverse transcriptases with little, if any, effect on the cellular enzymes. 3'-Azido-2',3'-dideoxythymidine (AZT) triphosphate and the two dideoxynucleoside triphosphates, ddTTP and ddGTP, inhibited HIV-1 reverse transcriptase to the same degree as Carbovir triphosphate, but were less selective in that they also inhibited DNA polymerases beta and gamma. We conclude that Carbovir is a highly selective antiretroviral agent.
  • Keywords

  • DNA Primase, Deoxyguanine Nucleotides, Dideoxynucleosides, Dideoxynucleotides, HIV, Humans, Nucleic Acid Synthesis Inhibitors, RNA Nucleotidyltransferases, Reverse Transcriptase Inhibitors, Thymine Nucleotides, Zidovudine
  • Pubmed Id

  • 19625909
  • Authorlist

  • White EL; Parker WB; Macy LJ; Shaddix SC; McCaleb G; Secrist JA; Vince R; Shannon WM
  • Start Page

  • 393
  • End Page

  • 398
  • Volume

  • 161
  • Issue

  • 2