Phosphonate Analogues of Diadenosine Tetraphosphate as Substrates and Inhibitors of Artemia Dinucleoside Tetraphosphatase

  • Alexander G. McLennan
  • Graham E. Taylor
  • Mark Prescott
  • G. Michael Blackburn
Part of the NATO ASI Series book series (NSSA, volume 174)


P1,P4 -bis(5′-nucleosidyl) tetraphosphate pyrophosphohydrolase (dinucleoside tetraphosphatase, Np4Nase, E.C. is believed to be responsible for the catabolism of the proposed signal nucleotide P1,P4 -bis(5′-adenosyl) tetraphosphate (diadenosine tetraphosphate, Ap4A) and related compounds in a wide variety of cell types. It is also a candidate for the enzyme involved in the degradation of the purine ring store Gp4G during pre-emergence and early larval development in Artemia (see accompanying paper[1] for detailed discussion and references).


Adenylate Kinase Ammonium Phosphate Binding Inter Tetrabutylammonium Salt Early Larval Development 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    M. Prescott, A. D. Milne and A. G. McLennan, Enzymes of dinucleoside oligophosphate metabolism in Artemia cysts and larvae;, accompanying article this volume.Google Scholar
  2. 2.
    M. Prescott and A. G. McLennan, The protein kinase activity associated with the major bis(5’-adenosyl) tetraphosphate-binding protein of Artemia, in “Artemia Research and its Applications, Vol. 2, Physiology, Biochemistry, Molecular Biology,” W. Decleir, L. Moens, H. Siegers, E. Jaspers and P. Sorgeloos, eds., Universa Press, Wetteren, Belgium (1987).Google Scholar
  3. 3.
    G. M. Blackburn, G. E. Taylor, G. R. J. Thatcher, M. Prescott and A. G. McLennan, Synthesis and resistance to enzymic hydrolysis of stereochgmically-defined phosphonate and thiophosphate analogues of P1, P4-bis(5’-adenosyl) tetraphosphate, Nucleic Acids Res. 15:6991 (1987).PubMedCrossRefGoogle Scholar
  4. 4.
    A. Guranowski, A. Biryukov, N. B. Tarussova, R. M. Khomutov and H. Jakubowski, Phosphonate analogues of diadenosine 5’, 5“’-P1,P4-tetraphosphate as Substrates and inhibitors of procaryotic and eucaryotic enzymes degrading dinucleoside tetraphosphates, Biochemistry 26:3425 (1987).PubMedCrossRefGoogle Scholar
  5. 5.
    L. D. Barnes and C. Culver, Isolation and characterization of diadenosine-5’, 5“’-P1, P4-tetraphosphate pyrophosphohydrolase from Physarum polycephalum, Biochemistry 21:6123 (1982).PubMedCrossRefGoogle Scholar
  6. 6.
    K.-H. Scheit, “Nucleotide Analogs: Synthesis and Biological Function,” J. Wiley and Sons, New York (1980).Google Scholar
  7. 7.
    G. M. Blackburn, T. D. Perree, A. Rashid, C. Bisbai and B. Lebleu, Chemica Scripta 26:21 (1986).Google Scholar
  8. 8.
    G. M. Blackburn, G. E. Taylor, R. H. Tattershall, G. R. J. Thatcher and A. G. McLennan, Phosphonate analogues of biological phosphates, in: “Biophosphates and Their Analogues — Synthesis, Structure, Metabolism and Activity,” K. S. Bruzik and W. J. Stec, eds., Elsevier, Amsterdam (1987).Google Scholar
  9. 9.
    Y. C. Cheng and W. H. Prusoff, Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 per cent infeibition (I50) of an enzymatic reaction, Biochem. Pharmacol. 22:3099 (1973).PubMedCrossRefGoogle Scholar
  10. 10.
    A. R. Fersht, Catalysis, binding and enzyme-substrate complementarity, Proc. R. Soc. London B 187:397 (1974).CrossRefGoogle Scholar
  11. 11.
    A. J. Guranowski, Specific enzymes degrading diadenosine tetraphosphate, Nucleosides and Nucleotides 6:307 (1987).CrossRefGoogle Scholar
  12. 12.
    T. I. Merkulova, M. K. Nurbekov, N. B. Tarussova and G. K. Kovaleva, Studies of ATP-and PPi-binding sites of bovine tryptophanyl-tRNA synthetase with the use of Ap4A-phosphonate analogues, Biopolymers and Cell 2:179 (1986).CrossRefGoogle Scholar
  13. 13.
    N. B. Tarussova, T. I. Osipova, T. V. Tyrtysh and A. I. Biryukov, Phosphonate analogues of P1, P4-bis(5’-adenosyl) tetraphosphate (Ap4A), in: “Biophosphates and Their Analogues — Synthesis, Structure, Metabolism and Activity,” K. S. Bruzik and W. J. Stec, eds., Elsevier, Amsterdam (1987).Google Scholar
  14. 14.
    H. Suzuki, Y. Tanaka, D. T. Buonamassa, B. Farina and E. Leone, inhibition of ADP-ribosylation of histone H1 by analogs of diadenosine 5’, 5“’-p1, p4-tetraphosphate, Mol. Cell. Biochem. 74:17 (1987).PubMedCrossRefGoogle Scholar
  15. 15.
    M. Prescott and A. G. McLennan, unpublished results.Google Scholar
  16. 16.
    R. Bone, Y. C. Cheng and R. Wolfenden, Inhibition of adenosine and thymidylate kinases by bisubstrate analogues, J. Biol. Chem. 261:16410 (1986).PubMedGoogle Scholar
  17. 17.
    P. Feldhaus, T. Fröhlich, R. S. Goody, M. Isakov and R. H. Schirmer, Synthetic inhibitors of adenylate kinases in the assays for ATPases and phosphokinases, Eur. J. Biochem. 57:197 (1975).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Alexander G. McLennan
    • 1
  • Graham E. Taylor
    • 1
    • 2
  • Mark Prescott
    • 1
  • G. Michael Blackburn
    • 1
    • 2
  1. 1.Department of BiochemistryUniversity of LiverpoolLiverpoolUK
  2. 2.Department of ChemistryUniversity of SheffieldSheffieldUK

Personalised recommendations