Novel nucleotide analogues as potential substrates for TMPK, a key enzyme in the metabolism of AZT.
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.
Müller
H C
HC
Institute of Organic Chemistry, University of Hamburg, Hamburg, Germany.
Meier
C
C
Balzarini
J
J
Reinstein
J
J
D001711:Biotransformation; D054306:Dideoxynucleotides; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors*; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013938:Thymidine Monophosphate / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013942:Thymine Nucleotides / Q000493:pharmacokinetics; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
D054306:Dideoxynucleotides; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009711:Nucleotides; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; C057287:3'-azido-3'-deoxythymidine 5'phosphate; D013938:Thymidine Monophosphate; D015215:Zidovudine; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase