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Thymidylate Synthase and Fluorouracil

  • Kathryn M. Ivanetich
  • Daniel V. Santi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 131)

Abstract

A knowledge of the catalytic mechanism of thymidylate synthase (TS), and its inhibition by 5-fluorodeoxyuridylate (FdUMP) was instrumental in developing the FUra-CF combination for cancer chemotherapy. The generation of the ideas which led to the current combination cleary demonstrates the importance of a fundamental knowledge of the interactions of inhibitors with their targets, and of how basic studies can be translated to clinical practice. The history of the development of the FUra-CF combination is a paradigm for the rational development of chemotherapeutic regimens. This report summarizes current knowledge of (a) the enzymology of the interaction of TS with FdUMP, (b) the 3-dimensional structure of TS, and (c) the effect of FUra on tRNA-uracil methyltranferase. Also, we suggest a possible molecular mechanism for the RNA effects of FUra.

Keywords

Carbon Unit Covalent Complex Covalent Adduct Covalent Bond Formation Pyrimidine Nucleotide Biosynthesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Kathryn M. Ivanetich
    • 1
  • Daniel V. Santi
    • 1
  1. 1.Departments of Biochemistry and Biophysics and Pharmaceutical Chemistry, and the Biomolecular Resource CenterUniversity of California, San FranciscoSan FranciscoUSA

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