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Stable analogues of coenzyme-substrate complex of spermidine/spermine-N 1-acetyltransferase reaction. Synthesis and interaction with the enzyme

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Abstract

A convenient two-step synthesis of conjugates of HS-CoA and D-pantetheine with aminooxy analogues of Spm and Spd was suggested. The use of acetone linker provided target conjugates with quantitative yields. The activity of CoA-derived “bisubstrate” inhibitors, being active at microM concentrations, was at least 100 times better than that of corresponding derivatives of D-pantetheine.

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Abbreviations

CoASH and CoASAc:

coenzyme A and its acetyl derivative

D-Pant:

N-(D-pantothenyl)aminoethyl mercaptan

Put:

putrescine (1,4-diaminobutane)

Spm:

spermine (1,12-diamino-4,9-diazadodecane)

nor-Spd:

nor-spermidine (1,7-diamino-4-azaheptane)

Spd:

spermidine (1,8-diamino-4-azaoctane)

SSAT:

spermidine/spermine-N 1-acetyltransferase

References

  1. Wolfenen, R., Bioorg. Med. Chem., 1999, vol. 7, pp. 647–652.

    Article  Google Scholar 

  2. Müller, I.B., Wu, F., Bergmann, B., Knockel, J., Walter, R.D., Gehring, H., and Wrenger, C., PLoS ONE, 2009, vol. 4, p. e4406.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  3. Khomutov, R.M., Dixon, H.B., Vdovina, L.V., Kirpichnikov, M.P., Morozov, Y.V., Severin, E.S., and Khurs, E.N., Biochem. J., 1971, vol. 124, pp. 99–106.

    PubMed Central  PubMed  CAS  Google Scholar 

  4. Somu, R.V., Boshoff, H., Qiao, C., Bennett, E.M., Barry, C.E.III., and Aldrich, C.C., J. Med. Chem., 2006, vol. 49, pp. 31–34.

    Article  PubMed  CAS  Google Scholar 

  5. Kappler, F., Vrudhula, V.M., and Hampton, A., J. Med. Chem., 1987, vol. 30, pp. 1599–1603.

    Article  PubMed  CAS  Google Scholar 

  6. Hickman, A.B., Namboodiri, M.A.A., Klein, D.C., and Dyda, F., Cell, 1999, vol. 97, pp. 361–369.

    Article  PubMed  CAS  Google Scholar 

  7. Brown, M.J.B., Mensah, L.M., Doyle, M.L., Broom, N.J.P., Osbourne, N., Forrest, A.K., Richardson, C.M., O’Hanlon, P.J., and Pope, A.J., Biochemistry, 2000, vol. 39, pp. 6003–6011.

    Article  PubMed  CAS  Google Scholar 

  8. Yu, M., Magalhaes, M.L.B., Cook, P.F., and Blanchard, J.S., Biochemistry, 2006, vol. 45, pp. 14788–14794.

    Article  PubMed  CAS  Google Scholar 

  9. Cullis, P.M., Wolfenden, R., Cousens, L.S., and Alberts, B.M., J. Biol. Chem., 1982, vol. 257, pp. 12165–12169.

    PubMed  CAS  Google Scholar 

  10. Ervin, B., Persson, L., and Pegg, A.E., Biochemistry, 1984, vol. 23, pp. 4250–4255.

    Article  Google Scholar 

  11. Hegde, S.S., Chandler, J., Vetting, M.W., Yu, M., and Blanchard, J.S., Biochemistry, 2007, vol. 46, pp. 7187–7195.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Wu, R., Saab, N.H., Hyang, H., Wiest, L., Pegg, A.E., Casero, R.A., and Woster, P.M., Bioorg. Med. Chem., 1996, vol. 4, pp. 825–836.

    Article  PubMed  CAS  Google Scholar 

  13. Libby, P.R. and Porter, C.W., Biochem. Pharmacol., 1992, vol. 44, pp. 830–832.

    Article  PubMed  CAS  Google Scholar 

  14. Fierke, C.A. and Jencks, W.P., J. Biol. Chem., 1986, vol. 261, pp. 7603–7606.

    PubMed  CAS  Google Scholar 

  15. Khomutov, A.R., Vepsalainen, J., Shvetsov, A.S., Hyvonen, T., Keinanen, T.A., Pustobaev, V.N., Eloranta, T.O., and Khomutov, R.M., Tetrahedron, 1996, vol. 52, pp. 13751–13766.

    Article  CAS  Google Scholar 

  16. Khomutov, A.R., Svetsov, A.S., Vepsalainen, J.J., and Kritzyn, A.M., Tetrahedron Lett., 2001, vol. 42, pp. 2887–2889.

    Article  CAS  Google Scholar 

  17. Simonyan, A.R., Vepsalainen, J., and Khomutov, A.R., Russ. J. Bioorg. Chem, 2006, vol. 32, pp. 578–585.

    Article  CAS  Google Scholar 

  18. Casero, R.A. and Marton, L.J., Nat. Rev. Drug Discov., 2007, vol. 6, pp. 373–390.

    Article  PubMed  CAS  Google Scholar 

  19. Seiler, N., Curr. Drug Targets, 2003, vol. 4, pp. 537–564.

    Article  PubMed  CAS  Google Scholar 

  20. Wallace, H.M. and Fraser, A.V., Amino Acids, 2004, vol. 26, pp. 353–365.

    Article  PubMed  CAS  Google Scholar 

  21. Casero, R.A. and Woster, P.M., J. Med. Chem., 2009, vol. 52, pp. 4551–4573.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Roblot, G., Wylde, R., Martin, A., and Parello, J., Tetrahedron, 1993, vol. 29, pp. 6381–6398.

    Article  Google Scholar 

  23. Della, RagioneF. and Pegg, A.E., Biochemistry, 1982, vol. 21, pp. 701–707.

    Article  Google Scholar 

  24. Khomutov, A.R., Biokhimiya, 2002, vol. 67, pp. 1403–1412.

    Google Scholar 

  25. Weisell, J., Hyvonen, M.T., Alhonen, L., Vepsalainen, J., Keinanen, T.A., and Khomutov, A.R., Curr. Pharm. Design, May 16 [Epub ahead of print] (in press).

  26. Ellman, G.L., Arch. Biochem. Biophys., 1959, vol. 82, pp. 70–77.

    Article  PubMed  CAS  Google Scholar 

  27. Bernacki, R.J., Oberman, E.J., Seweryniak, K.E., Atwood, A., Bergeron, R.J., and Porter, C.W., Clin. Cancer Res,, 1995, vol. 1, pp. 847–857.

    PubMed  CAS  Google Scholar 

  28. Cox, B.G. and Hammes, G.G., Proc. Natl., Acad. Sci. U.S.A., 1983, vol. 80, pp. 4233–4237.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland

    T. A. Keinanen & J. Vepsalainen

  2. Virtanen Institute of Molecular Sciences, University of Eastern Finland, Kuopio, Finland

    T. Hyvonen, L. Alhonen & J. Janne

  3. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov St., 32, Moscow, 119991, Russia

    A. R. Khomutov

Authors
  1. T. A. Keinanen
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  2. T. Hyvonen
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  3. J. Vepsalainen
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  4. L. Alhonen
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  5. A. R. Khomutov
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  6. J. Janne
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Corresponding author

Correspondence to A. R. Khomutov.

Additional information

Original Russian Text © T.A. Keinanen, T. Hyvonen, J. Vepsalainen, L. Alhonen, A.R. Khomutov, J. Janne, 2014, published in Bioorganicheskaya Khimiya, 2014, Vol. 40, No. 2, pp. 170–177.

The article was translated by the authors.

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Keinanen, T.A., Hyvonen, T., Vepsalainen, J. et al. Stable analogues of coenzyme-substrate complex of spermidine/spermine-N 1-acetyltransferase reaction. Synthesis and interaction with the enzyme. Russ J Bioorg Chem 40, 155–161 (2014). https://doi.org/10.1134/S1068162014020071

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  • DOI: https://doi.org/10.1134/S1068162014020071

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