Article
Tolerance of 5-fluorodeoxyuridine resistant human thymidylate synthases to alterations in active site residues.
Nucleic acids research - 15 Sept 1999
Landis D M, Gerlach J L, Adman E T, Loeb L A
Abstract excerpt
Fluoropyrimidines, such as 5-fluorouracil (5-FU), are used extensively in cancer therapy. In the cell, 5-FU is metabolized to 5-fluorodeoxyuridylate (5-FdUMP), a tight binding covalent inhibitor of thymidylate synthase (TS). In order to create 5-FdUMP resistant enzymes to protect chemosensitive normal cells and further understand mechanisms of 5-FdUMP resistance, we have randomized four residues within the active...
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