Structural determinants of HIV-1 reverse transcriptase stereoselectivity towards (beta)-L-deoxy- and dideoxy-pyrimidine nucleoside triphosphates: molecular basis for the combination of L-dideoxynucleoside analogs with non-nucleoside inhibitors in anti HIV chemotherapy

Nucleosides Nucleotides. 1999 Apr-May;18(4-5):795-805. doi: 10.1080/15257779908041566.


We have compared the HIV-1 RT mutants containing the single substitutions L100I, K103N, V106A, V179D, Y181I and Y188L, known to confer NNI-resistance in treated patients, to HIV-1 RT wt for their sensitivity towards inhibition by D- and L-deoxy- and dideoxy-nucleoside tiphosphates. The results showed a differential effect of the substitutions on the affinity for both D- and L-enantiomers of deoxy- and dideoxy-nucleoside triphosphates and provide a rationale for the utilization of L-dideoxynucleoside analogs with NNI in combination chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / metabolism*
  • Anti-HIV Agents / therapeutic use
  • Binding Sites
  • Dideoxynucleosides / administration & dosage
  • Dideoxynucleosides / therapeutic use
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / genetics
  • HIV Reverse Transcriptase / metabolism*
  • Humans
  • Kinetics
  • Mutation
  • Protein Structure, Secondary
  • Pyrimidine Nucleotides / administration & dosage
  • Pyrimidine Nucleotides / metabolism*
  • Pyrimidine Nucleotides / therapeutic use
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / metabolism*
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Stereoisomerism


  • Anti-HIV Agents
  • Dideoxynucleosides
  • Pyrimidine Nucleotides
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase