Abstract
To determine how modifications of 5-fluoro-dUMP (FdUMP), a thymidylate synthase (EC 2.1.1.45) chemotherapeutically active inhibitor, may affect its specificity, a study was conducted on inhibition of the enzyme from parental (L1210P) and 5-fluoro-dUrd-resistant (L1210R) mouse leukemia L1210 cells, the tapeworm Hymenolepis diminuta (H.d.) and regenerating rat liver (RRL) by FdUMP and its 2-thio-and 4-thio-congeners. The enzymes differed in sensitivity to time-and methylenetetrahydrofolate-dependent inactivation by FdUMP, with Ki values ranging from 10-9 M for the L1210P and 10-8 M for the L1210R1 and RRL enzymes,2 to 10-7 M for the H.d. enzyme.2
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Dzik, J.M. et al. (1993). Interaction with 2(4)-Thio-5-Fluoro-dUMP of Thymidylate Synthases with Differing Sensitivities to 5-Fluoro-dUMP. In: Ayling, J.E., Nair, M.G., Baugh, C.M. (eds) Chemistry and Biology of Pteridines and Folates. Advances in Experimental Medicine and Biology, vol 338. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2960-6_127
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DOI: https://doi.org/10.1007/978-1-4615-2960-6_127
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