Novel nucleotide analogues as potential substrates for TMPK, a key enzyme in the metabolism of AZT

Nucleosides Nucleotides Nucleic Acids. 2003 May-Aug;22(5-8):821-3. doi: 10.1081/NCN-120022662.

Abstract

Novel cyclic and acyclic analogues of dTMP and AZTMP were synthesized from the corresponding cycloSal-phosphotriesters. This method yielded the nucleotides in good yields with a simple work-up. Investigation of the substrate properties of the modified nucleotides towards TmpK showed, that they are very poor substrates for this key enzyme in the bioactivation of AZT.

MeSH terms

  • Biotransformation
  • Dideoxynucleotides
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indicators and Reagents
  • Kinetics
  • Nucleoside-Phosphate Kinase / antagonists & inhibitors*
  • Nucleotides / chemical synthesis*
  • Nucleotides / chemistry
  • Nucleotides / pharmacokinetics*
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacokinetics
  • Thymidine Monophosphate / chemical synthesis*
  • Thymidine Monophosphate / pharmacokinetics
  • Thymine Nucleotides / pharmacokinetics
  • Zidovudine / analogs & derivatives*
  • Zidovudine / pharmacokinetics*

Substances

  • Dideoxynucleotides
  • Enzyme Inhibitors
  • Indicators and Reagents
  • Nucleotides
  • Reverse Transcriptase Inhibitors
  • Thymine Nucleotides
  • 3'-azido-3'-deoxythymidine 5'phosphate
  • Thymidine Monophosphate
  • Zidovudine
  • Nucleoside-Phosphate Kinase
  • dTMP kinase