Monitoring the Intracellular Metabolism of Nucleoside Phosphoramidate Pronucleotides by 31P NMR

Jisook Kim, Daniel P. Drontle, Carston R. Wagner

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The intracellular metabolism of 3′-azido-3′-deoxythymidine (AZT)-(L)-tryptophan methyl ester phosphoramidate (L-ATO) and AZT-(L)-phenylalanine methyl ester phosphoramidate (L-APO) by the human T-lymphoblastoid cell line CCRF-CEM (CEM-1.3) and peripheral blood mononuclear cell line (PBMC) was investigated with high field 31P NMR spectroscopy. The AZT amino acid phosphoramidates were shown to accumulate intracellularly and to be readily converted into AZT-MP by both tissues types. Thus, the efficient delivery of nucleoside monophosphates to cells can be facilitated by nucleoside phosphoramidate pronucleotides.

Original languageEnglish (US)
Pages (from-to)483-493
Number of pages11
JournalNucleosides, Nucleotides and Nucleic Acids
Volume23
Issue number1-2
DOIs
StatePublished - 2004

Bibliographical note

Funding Information:
The authors are thankful to Dr. Balfour’s group in ACTU unit in the Department of Lab-medicine and Pathology at the University of Minnesota for providing PBMCs. We are also grateful to Dr. David Live and Dr. Beverly Ostrowski for their assistance in NMR technique. NMR instrumentation was provided with funds from the NSF (BIR-961477), the University of Minnesota Medical Scholl, and the Minnesota Medical Foundation. This research is supported by NIH-NCI (CA 89615).

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • AZT
  • Antiviral agent
  • P NMR
  • Phosphoramidate
  • Prodrugs

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