2-fluoro-ATP: a toxic metabolite of 9-beta-D-arabinosyl-2-fluoroadenine.
Murine P388 cells incubated in vitro with the anticancer drug arabinosyl 2-fluoroadenine accumulate its 5'-triphosphate, F-araATP, as the major phosphorylated metabolite. A new chromatographically separate metabolite that accumulated to levels 10% of that of F-araATP was identified as 2-fluoro-ATP, by the following criteria. 1. The metabolite coeluted with the authentic compound on anion-exchange HPLC. 2. Dephosphorylation of the metabolite yielded a compound that was chromatographically identical to 2-fluoroadenosine. 3. The compound was sensitive to NaIO4 oxidation. Cellular incubation experiments indicated that 2-fluoroadenine, but not arabinosyl 2-fluorohypoxanthine, was the likely intermediate in the formation of 2-fluoro-ATP.
D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001088:Arabinonucleotides / Q000378:metabolism; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D007941:Leukemia P388 / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism*; D051379:Mice; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000378:metabolism
D001088:Arabinonucleotides; C038022:2-fluoro-ATP; C038208:2-fluoroadenine; C034957:2-fluoro-araATP; D000255:Adenosine Triphosphate; D014740:Vidarabine; D000225:Adenine; C024352:fludarabine