Assignment and pH dependence of the 19F-NMR resonances from the fluorouracil anabolites involved in fluoropyrimidine chemotherapy
✍ Scribed by Norbert W. Lutz; William E. Hull
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 141 KB
- Volume
- 12
- Category
- Article
- ISSN
- 0952-3480
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✦ Synopsis
Fluoropyrimidine chemotherapy relies on the intracellular anabolic conversion of 5-fluorouracil and the corresponding nucleosides to cytotoxic fluorinated nucleotides (F-Nuctd), such as 5-fluorouridine-5'-triphosphate (FUTP) or 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), which can be detected by 19 F-NMR spectroscopy. We have made 19 F-NMR signal assignments at 11.7 T and 4 °C for model solutions containing 5-fluorouracil (FUra), 5-fluorouridine (FUrd), 5-fluoro-2'-deoxyuridine (FdUrd), 5-fluorouridine-5'-monophosphate (FUMP), FdUMP, 5fluorouridine-5'-diphosphate (FUDP), FUTP and 5-fluorouridine-5'-diphospho(1)-a-D-glucose (FUDPG), and we have studied the effects of pH over the range 4.5-7.8, of Mg 2 concentration and addition of EDTA. This information provides a basis for the analysis of 19 F-NMR spectra obtained from cells, tissues or extracts following fluoropyrimidine treatment.