Kinetics of inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase by the novel HIV-1-specific nucleoside analogue [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5 "- (4"-amino-1",2"-oxathiole-2",2"-dioxide)thymine (TSAO-T)

J Biol Chem. 1992 Jun 15;267(17):11831-8.


[2',5'-Bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro- 5"-(4"-amino-1",2"-oxathiole-2", 2"-dioxide)thymine (TSAO-T) is a representative of a novel class of nucleoside analogues that are endowed with a potent and specific activity against human immunodeficiency virus (HIV) type 1 and are targeted at the HIV-1 reverse transcriptase (RT). Inhibition of HIV-1 RT by TSAO-T was reversible and noncompetitive with respect to dGTP as the substrate and poly(C).oligo(dG) as the template/primer. In contrast with the nonnucleoside derivatives tetrahydroimidazo-[4,5,1-jk][1,4]- benzodiazepin-2(1H)-thione (TIBO) (R-82150), nevirapine (BI-RG-587) and the HEPT derivative I-HEPU-SdM, TSAO-T was not inhibitory to HIV-1 RT in the presence of other homopolymeric template/primers. It did not interfere with the DNA-dependent DNA polymerase function of HIV-1 RT, HIV-2 RT, herpes simplex virus type 1 DNA polymerase, or Taq polymerase. However, TSAO-T proved inhibitory to the HIV-1 RT reaction primed by Escherichia coli 16S/23S rRNA, irrespective of the nature of the radiolabeled 2'-deoxynucleotide 5'-triphosphate (dNTP) used. TSAO-T does not act as a DNA chain terminator. It interacts with HIV-1 RT at a nonsubstrate (dNTP)-binding site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Benzodiazepines / pharmacology
  • Benzoxazoles / pharmacology
  • Deoxyguanine Nucleotides / pharmacology
  • HIV Reverse Transcriptase
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Imidazoles / pharmacology
  • Kinetics
  • Nevirapine
  • Pyridines / pharmacology
  • Pyridones / pharmacology
  • RNA-Directed DNA Polymerase / metabolism
  • Reverse Transcriptase Inhibitors*
  • Templates, Genetic
  • Thiouracil / analogs & derivatives*
  • Thiouracil / pharmacology


  • Antiviral Agents
  • Benzoxazoles
  • Deoxyguanine Nucleotides
  • Imidazoles
  • Pyridines
  • Pyridones
  • Reverse Transcriptase Inhibitors
  • R 82150
  • Benzodiazepines
  • L 697639
  • 5-isopropyl-1-((hydroxyethoxy)methyl)-6-(3,5-dimethylphenythio)-2-thiouracil
  • Thiouracil
  • Nevirapine
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase