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Enzyme Inhibition by Phosphonate Analogues of dTTP

  • S. E. Barrie
  • R. M. Paine
  • J. A. Stock
  • R. B. Vincent
  • K. R. Harrap
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)

Abstract

Ribonucleotide reductase (RR) (EC 1.17.4.1), deoxycytidylate deaminase (dCMP DA) (EC 3.5.4.12) and thymidine kinase (TK) (EC 2.7.1.2) are important enzymes for the production of thymidine nucleotides, and are subject to feedback regulation by dTTP. Analogues of dTTP which mimic this regulatory behaviour might be useful inhibitors of both the de novo and salvage pathways of thymidylate biosynthesis. We have prepared and tested three phosphonate analogues of dTTP, αβ-methylene-dTTP (αβ-CH2-dTTP), βγ -methylene-dTTP (βγ-CH2-dTTP) and αβ,βγ-dimethylene-dTTP (αβ, βγ-CH2-dTTP) for inhibitory activity against these enzymes from L1210 cells.

Keywords

Thymidine Kinase Ribonucleotide Reductase Salvage Pathway Pyridoxal Phosphate Ammonium Sulphate Fraction 
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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References

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    J.G. Cory and M.M. Mansell, Studies on mammalian ribonucleotide reductase inhibition by pyridoxal phosphate and the dialdehyde derivatives of adenosine, adenosine 5′-monophosphate and adenosine 5′-triphosphate, Cancer Res. 35: 390 (1975).PubMedGoogle Scholar
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    G.F. Maley and F. Maley, The purification and properties of deoxycytidylate deaminase from chick embryo extracts, J. Biol. Chem. 239: 1168 (1964)Google Scholar
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    E.P. Kowal and G. Markus, Affinity chromatography of thymidine kinase from a rat colon adenocarcinoma, Prep. Biochem. 6: 369 (1976).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • S. E. Barrie
    • 1
  • R. M. Paine
    • 1
  • J. A. Stock
    • 1
  • R. B. Vincent
    • 1
  • K. R. Harrap
    • 1
  1. 1.Department of Biochemical PharmacologyInstitute of Cancer ResearchSutton, SurreyEngland

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