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Thiacalix[4]arene as molecular platform for design of alkaline phosphatase inhibitors

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Abstract

Effect of thiacalix[4]arene platform on inhibition of alkaline phosphatase by macrocyclic phosphonate is presented in this article. Using tetrakis(dihydroxyphosphorylmethyl) derivatives we have found that phosphonate inhibitor on thiacalix[4]arene platform has displayed stronger inhibition properties towards alkaline phosphatases from bovine intestine mucosa, shrimp and human placenta than its structural calix[4]arene analogue. For elucidation of the molecular mechanism of the inhibition the tested macrocyclic compounds were docked computationally to the active site of alkaline phosphatase from shrimp. The role of thiacalix[4]arene platform in formation of the enzyme-inhibitor complex is discussed.

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Thiacalix[4]arene as molecular platform for design of alkaline phosphatase inhibitors

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References

  1. Engel, R.: Phosphonates as analogues of natural phosphates. Chem. Rev. 77, 349–367 (1977)

    Article  CAS  Google Scholar 

  2. Hilderbrand, R.L.: The Role of Phosphonates in Living Systems. Boca Raton FL, CRC Press (1983)

    Google Scholar 

  3. Kukhar, V.P., Hudson, H.R. (eds.): Aminophosphonic and aminophosphinic acids: chemistry and biological activity. Wiley, LTD Inc., Chichester, UK (2000)

    Google Scholar 

  4. Rogers, M.J., Gordon, S., Benford, H.L., Coxon, F.P., Luckman, S.P., Monkkonen, J., Frith, J.C.: Cellular and molecular mechanisms of action of bisphosphonates. Cancer 88, 2961–2978 (2000)

    Article  CAS  Google Scholar 

  5. Bergstrom, J.D., Bostedor, R.G., Masarachia, P.J., Reszka, A.A., Rodan, G.: Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch. Biochem. Biophys. 373, 231–241 (2000)

    Article  CAS  Google Scholar 

  6. Bukowski, J.F., Dascher, C.C., Das, H.: Alternative bisphosphonate targets and mechanisms of action. Biochem. Biophys. Res. Commun. 328, 746–750 (2005)

    Article  CAS  Google Scholar 

  7. Vovk, A.I., Kalchenko, V.I., Cherenok, S.A., Kukhar, V.P., Muzychka, O.V., Lozynsky, M.O.: Calix[4]arene methylenebisphosphonic acids as calf intestine alkaline phosphatase inhibitors. Org. Biomol. Chem. 2, 3162–3166 (2004)

    Article  CAS  Google Scholar 

  8. Cherenok, S., Vovk, A., Muravyova, I., Shivanyuk, A., Kukhar, V., Lipkowski, J., Kalchenko, V.: Calix[4]arene α-aminophosphonic acids: asymmetric synthesis and enantioselective inhibition of an alkaline phosphatase. Org. Lett. 8, 549–552 (2006)

    Article  CAS  Google Scholar 

  9. Le Du, M.H., Millan, J.L.: Structural evidence of functional divergence in human alkaline phosphatases. J. Biol. Chem. 277, 49808–49814 (2002)

    Article  CAS  Google Scholar 

  10. Zhang, L., Balcerzak, M., Radisson, J., Thouverey, C., Pikula, S., Azzar, G., Buchet, R.: Phosphodiesterase activity of alkaline phosphatase in ATP-initiated Ca(2 +) and phosphate deposition in isolated chicken matrix vesicles. J. Biol. Chem. 280, 37289–37296 (2005)

    Article  CAS  Google Scholar 

  11. Coburn, S.P., Mahuren, J.D., Jain, M., Zubovic, Y., Wortsman, J.: Alkaline phosphatase (EC 3.1.3.1) in serum is inhibited by physiological concentrations of inorganic phosphate. J. Clin. Endocrinology and Metabolism. 83, 3951–3957 (1998)

    Article  CAS  Google Scholar 

  12. Mathieu, P., Voisine, P., Pepin, A., Shetty, R., Savard, N., Dagenais, F.: Calcification of human valve interstitial cells is dependent on alkaline phosphatase activity. J. Heart Valve Dis. 14, 353–357 (2005)

    Google Scholar 

  13. Sanchez de Medina, F., Martinez-Augustin, O., Gonzalez, R., Ballester, I., Nieto, A., Galvez, J., Zarzuelo, A.: Induction of alkaline phosphatase in the inflamed intestine: a novel pharmacological target for inflammatory bowel disease. Biochem. Pharmacol. 68, 2317–2326 (2004)

    Article  CAS  Google Scholar 

  14. Tung, C.B., Tung, C.F., Yang, D.Y., Hu, W.H., Hung, D.Z., Peng, Y.C., Chang, C.S.: Extremely high levels of alkaline phosphatase in adult patients as a manifestation of bacteremia. Hepatogastroenterology 52, 1347–1350 (2005)

    CAS  Google Scholar 

  15. Holtz, K.M., Stec, B., Kantrowitz, E.R.: A model of the transition state in the alkaline phosphatase reaction. J. Biol. Chem. 274, 8351–8354 (1999)

    Article  CAS  Google Scholar 

  16. Holtz, K.M., Stec, B., Myers, J.K., Antonelli, S.M., Widlanski, T.S., Kantrowitz, E.R.: Alternate modes of binding in two crystal structures of alkaline phosphatase-inhibitor complexes. Protein Sci. 9, 907–915 (2000)

    Article  CAS  Google Scholar 

  17. Llinas, P., Stura, E.A., Menez, A., Kiss, Z., Stigbrand, T., Millan, J.L., Le Du, M.H.: Structural studies of human placental alkaline phosphatase in complex with functional ligands. J. Mol. Biol. 350, 441–451 (2005)

    Article  CAS  Google Scholar 

  18. Almi, M., Arduini, A., Casnati, A., Pochini, A., Ungaro, R.: Chloromethylation of calixarenes and synthesis of new water soluble macrocyclic hosts. Tetrahedron 45, 2177–2182 (1989)

    Article  CAS  Google Scholar 

  19. Kasyan, O., Swierczynski, D., Drapailo, A., Suwinska, K., Lipkowski, J., Kalchenko, V.: Upper rim substituted thiacalix[4]arenes. Tetrahedron Lett. 44, 7167–7170 (2003)

    Article  CAS  Google Scholar 

  20. Dixon, M., Webb, E.C.: Enzymes. Longman, London (1982). (in Russian, Mir, Moscow)

    Google Scholar 

  21. Morris, G.M., Goodsell, D.S., Huey, R., Olson, A.J.: Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4. J. Comput. Aided Mol. Des. 10, 293–304 (1996)

    Article  CAS  Google Scholar 

  22. Morris, G.M., Goodsel, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., Olson, A.J.: Automated docking using a Lamarckian genetic algorithm and empirical binding free energy function. J. Comput. Chem. 19, 1639–1662 (1998)

    Article  CAS  Google Scholar 

  23. de Backer, M.M., McSweeney, S., Lindley, P.F., Hough, E.: Ligand-binding and metal-exchange crystallographic studies on shrimp alkaline phosphatase. Acta Crystallogr. D Biol. Crystallogr. 60, 1555–1561 (2004)

    Article  Google Scholar 

  24. Stote, R.H., Karplus, M.: Zinc binding in proteins and solution: a simple but accurate nonbonded representation. Proteins 23, 12–31 (1995)

    Article  CAS  Google Scholar 

  25. Case, D.A., Pearlman, D.A., Caldwell, J.W., et al.: AMBER 7. University of California, San Francisco (2002)

    Google Scholar 

  26. Guex, N., Peitsch, M.C.: SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18, 2714–2723 (1997)

    Article  CAS  Google Scholar 

  27. Iki, N., Miyano, S.: Can thiacalixarene surpass calixarene? J. Incl. Phenom. Macrocycl. Chem. 41, 99–105 (2001)

    Article  CAS  Google Scholar 

  28. Grootenhuis, P.D.J., Kollman, P.A., Groenen, L.G., Reinhoudt, D.N., van Hummel, G.J., Ugozzoli, F., Andreetti, G.D.: Computational study of the structural, energetical, and acid-base properties of calix[4]arenes. J. Am. Chem. Soc. 112, 4165–4176 (1990)

    Article  CAS  Google Scholar 

  29. Groenen, L.G., Steinwender, E., Lutz, B.T.G., van der Maas, J.H., Reinhoudt, D.N.: Solvents effects on the conformations and hydrogen bond structure of partially methylated p-tret-butylcalix[4]arenes. J. Chem. Soc., Perkin Trans. 2, 1893–1898 (1992)

    Google Scholar 

  30. Manes, T., Hoylaerts, M.F., Muller, R., Lottspeich, F., Holke, W., Millan, J.L.: Genetic complexity, structure, and characterization of highly active bovine intestinal alkaline phosphatases. J. Biol. Chem. 273, 23353–23360 (1998)

    Article  CAS  Google Scholar 

  31. Hong, J., Ham, S.: Comparative study of calix[4]arene derivatives: implications for ligand design. Tetrahedron Lett. 49, 2393–2396 (2008)

    Article  CAS  Google Scholar 

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Acknowledgments

The authors greatly appreciate the possibility of using the calculation cluster of the Kyiv National Taras Shevchenko University. This research was supported by the National Academy of Sciences of Ukraine (A.I.V., L.A.K., V.P.K., grant 01/03-08). A.B.D. and V·I.K. thank the NASU-RFBR grant for partial support of the work.

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Authors and Affiliations

  1. Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, 02660, Kyiv-94, Ukraine

    A. I. Vovk, L. A. Kononets, V. Yu. Tanchuk & V. P. Kukhar

  2. Institute of Organic Chemistry, NAS of Ukraine, 02094, Kyiv-94, Ukraine

    A. B. Drapailo & V. I. Kalchenko

Authors
  1. A. I. Vovk
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  2. L. A. Kononets
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  3. V. Yu. Tanchuk
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  4. A. B. Drapailo
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  5. V. I. Kalchenko
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  6. V. P. Kukhar
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Correspondence to A. I. Vovk.

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Vovk, A.I., Kononets, L.A., Tanchuk, V.Y. et al. Thiacalix[4]arene as molecular platform for design of alkaline phosphatase inhibitors. J Incl Phenom Macrocycl Chem 66, 271–277 (2010). https://doi.org/10.1007/s10847-009-9607-9

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  • DOI: https://doi.org/10.1007/s10847-009-9607-9

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