Assignment and pH dependence of the F-19-NMR resonances from the fluorouracil anabolites involved in fluoropyrimidine chemotherapy

Fluoropyrimidine chemotherapy relies on the intracellular anabolic conversi on of 5-fluorouracil and the corresponding nucleosides to cytotoxic fluorin ated nucleotides (F-Nuctd), such as 5-fluorouridine-5'-triphosphate (FUTP) or 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), which can be detected by F-19-NMR spectroscopy. We have made F-19-NMR signal assignments at 11.7 T and 4 degrees C for model solutions containing 5-fluorouracil (FUra), 5- fluorouridine (FUrd), 5-fluoro-2'-deoxyuridine (FdUrd), 5-fluorouridine-5'- monophosphate (FUMP), FdUMP, 5-fluorouridine-5'-diphosphate (FUDP), FUTP an d 5-fluorouridine-5'-diphospho( 1)-alpha-D-glucose (FUDPG), and we have stu died the effects of pH over the range 4.5-7.8, of Mg2+ concentration and ad dition of EDTA. This information provides a basis for the analysis of F-19- NMR spectra obtained from cells, tissues or extracts following fluoropyrimi dine treatment. Copyright (C) 1999 John Wiley & Sons, Ltd.