Ukr.Biochem.J. 2015; Volume 87, Issue 4, Jul-Aug, pp. 24-31

doi: https://doi.org/10.15407/ubj87.04.024

Inhibitory potential of polyhydroxylated fullerenes against protein tyrosine phosphatase 1B

23.07.2015   Uncategorized   No comments

O. L. Kobzar, V. V. Trush, V. Yu. Tanchuk, A. I. Vovk

Institute of Bioorganic Chemistry and Petrochemistry,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: vovk@bpci.kiev.ua

Inhibition of PTP1B by polyhydroxylated fullerenes was studied in silico and in vitro. The enzyme kinetics in the presence of polyhydroxy small gap fullerenes showed that reciprocal value of maximum velocity non-linearly increases with increasing the inhibitor concentration. Analysis of the dose-dependent curve of PTP1B inhibition suggests an apparent positive cooperativity with involvement of at least two binding sites for the hydroxylated fullerene cages. Molecular docking calculations indicated that highly hydroxylated fullerene C60 may occupy the active site and additional allosteric binding site with similar affinity. In silico analysis of a number of fullerenols with 6, 12, 18, 24, 30, and 36 hydroxyl groups showed that the inhibitory activity may depend on the degree of hydroxylation of the nanoparticles surface. These data provide some understanding of the mechanisms of inhibitory action of fullerenols on activity of protein tyrosine phosphatases.

Keywords: , , ,

References:

  1. Zhu J, Ji Z, Wang J, Sun R, Zhang X, Gao Y, Sun H, Liu Y, Wang Z, Li A, Ma J, Wang T, Jia G, Gu Y. Tumor-inhibitory effect and immunomodulatory activity of fullerol C60(OH)x. Small. 2008 Aug;4(8):1168-75. PubMed, CrossRef
  2. Liu Y, Jiao F, Qiu Y, Li W, Qu Y, Tian C, Li Y, Bai R, Lao F, Zhao Y, Chai Z, Chen C. Immunostimulatory properties and enhanced TNF- alpha mediated cellular immunity for tumor therapy by C60(OH)20 nanoparticles. Nanotechnology. 2009 Oct 14;20(41):415102. PubMed, CrossRef
  3. Kojic V., Jakimov D., Bogdanovic G., Djordjevic A. Effects of fullerenol C60(OH)24 on cytotoxicity induced by antitumor drugs on human breast carcinoma cell lines. Mater Sci Forum. 2005;494:543-548. CrossRef
  4. Jiao F., Liu Y., Qu Y., Li W., Zhou G., Ge C., Li Y., Sun B., Chen Ch. Studies on anti-tumor and antimetastatic activities of fullerenol in a mouse breast cancer model. Carbon. 2010 Jul;48(8):2231-2243. CrossRef
  5. Trajković S, Dobrić S, Jaćević V, Dragojević-Simić V, Milovanović Z, Dordević A. Tissue-protective effects of fullerenol C60(OH)24 and amifostine in irradiated rats. Colloids Surf B Biointerfaces. 2007 Jul 1;58(1):39-43. PubMed, CrossRef
  6. Bogdanović V, Stankov K, Icević I, Zikic D, Nikolić A, Solajić S, Djordjević A, Bogdanović G. Fullerenol C60(OH)24 effects on antioxidative enzymes activity in irradiated human erythroleukemia cell line. J Radiat Res. 2008 May;49(3):321-7. PubMed, CrossRef
  7. Ueng TH, Kang JJ, Wang HW, Cheng YW, Chiang LY. Suppression of microsomal cytochrome P450-dependent monooxygenases and mitochondrial oxidative phosphorylation by fullerenol, a polyhydroxylated fullerene C60. Toxicol Lett. 1997 Sep 19;93(1):29-37. PubMed, CrossRef
  8. Meng X, Chen Z, Li B, Zhang Y, Zhao D, Yang X. Inhibition of M-MuLV reverse transcriptase activity by fullerene derivatives. Chin Sci Bull. 2006 Oct;51(20):2550-2. CrossRef
  9. Yang ST, Wang H, Guo L, Gao Y, Liu Y, Cao A. Interaction of fullerenol with lysozyme investigated by experimental and computational approaches. Nanotechnology. 2008 Oct 1;19(39):395101. PubMed, CrossRef
  10. Kotelnikova RA, Smolina AV, Grigoryev VV, Faingold II, Mischenko DV, Rybkin AYu, Poletayeva DA, Vankin GI, Zamoyskiy VL, Voronov II, Troshin PA, Kotelnikov A. I. Bachurin SO. Influence of water-soluble derivatives of [60]fullerene on therapeutically important targets related to neurodegenerative diseases. Med Chem Commun. 2014;5(11):1664-8. CrossRef
  11. Khakina EA, Yurkova AA, Peregudov AS, Troyanov SI, Trush VV, Vovk AI, Mumyatov AV, Martynenko VM, Balzarini J, Troshin PA. Highly selective reactions of C60Cl6 with thiols for the synthesis of functionalized [60]fullerene derivatives. Chem Commun (Camb). 2012 Jul 21;48(57):7158-60. PubMed, CrossRef
  12. Kobzar OL, Trush VV, Tanchuk VY, Zhilenkov AV, Troshin PA, Vovk AI. Fullerene derivatives as a new class of inhibitors of protein tyrosine phosphatases. Bioorg Med Chem Lett. 2014 Jul 15;24(14):3175-9. PubMed, CrossRef
  13. Kobzar OL, Trush VV, Tanchuk VYu, Voronov II, Peregudov AS, Troshin PA, Vovk AI. Polycarboxylic fullerene derivatives as protein tyrosine phosphatase inhibitors. Mendeleev Commun. 2015;25(3):199-201. CrossRef
  14. Hendriks WJ, Elson A, Harroch S, Pulido R, Stoker A, den Hertog J. Protein tyrosine phosphatases in health and disease. FEBS J. 2013 Jan;280(2):708-30. Epub 2012 Oct 1. Review. PubMed, CrossRef
  15. Goldstein BJ, Bittner-Kowalczyk A, White MF, Harbeck M. Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein. J Biol Chem. 2000 Feb 11;275(6):4283-9. PubMed, CrossRef
  16. Asante-Appiah E, Kennedy BP. Protein tyrosine phosphatases: the quest for negative regulators of insulin action. Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E663-70. Review. PubMed, CrossRef
  17. Zabolotny JM, Bence-Hanulec KK, Stricker-Krongrad A, Haj F, Wang Y, Minokoshi Y, Kim YB, Elmquist JK, Tartaglia LA, Kahn BB, Neel BG. PTP1B regulates leptin signal transduction in vivo. Dev Cell. 2002 Apr;2(4):489-95. PubMed, CrossRef
  18. Lessard L, Stuible M, Tremblay ML. The two faces of PTP1B in cancer. Biochim Biophys Acta. 2010 Mar;1804(3):613-9. Review. PubMed, CrossRef
  19. Bialy L, Waldmann H. Inhibitors of protein tyrosine phosphatases: next-generation drugs? Angew Chem Int Ed Engl. 2005 Jun 20;44(25):3814-39. Review. PubMed, CrossRef
  20. Sayes CM, Fortner JD, Guo W, Lyon D, Boyd AM, Ausman KD, Tao YJ, Sitharaman B, Wilson LJ, Hughes JB, West JL, Colvin VL. The differential cytotoxicity of water-soluble fullerenes. Nano Lett. 2004 Oct;4(10):1881-7. CrossRef
  21. Isakovic A, Markovic Z, Todorovic-Markovic B, Nikolic N, Vranjes-Djuric S, Mirkovic M, Dramicanin M, Harhaji L, Raicevic N, Nikolic Z, Trajkovic V. Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. Toxicol Sci. 2006 May;91(1):173-83. PubMed, CrossRef
  22. Mrdanović J, Solajić S, Bogdanović V, Stankov K, Bogdanović G, Djordjevic A. Effects of fullerenol C60(OH)24 on the frequency of micronuclei and chromosome aberrations in CHO-K1 cells. Mutat Res. 2009 Nov-Dec;680(1-2):25-30. PubMed, CrossRef
  23. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010 Jan 30;31(2):455-61. PubMed, PubMedCentral, CrossRef
  24. Rodriguez-Zavala J. G., Guirado-Lopez R. A. Structure and energetics of polyhydroxylated carbon fullerenes. Phys Rev B. 2004;69(7):075411. CrossRef
  25. Rodríguez-Zavala JG, Guirado-López RA. Stability of highly OH-covered C60 fullerenes: role of coadsorbed O impurities and of the charge state of the cage in the formation of carbon-opened structures. J Phys Chem A. 2006 Aug 3;110(30):9459-68. PubMed, CrossRef
  26. Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform. 2012 Aug 13;4(1):17. PubMed, PubMedCentral, CrossRef
  27. Coyuco JC, Liu Y, Tan BJ, Chiu GN. Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery. Int J Nanomedicine. 2011;6:2253-63. Epub 2011 Oct 10. PubMed, PubMed, CrossRef
  28. Brant JA, Labille J, Robichaud CO, Wiesner M. Fullerol cluster formation in aqueous solutions: implications for environmental release. J Colloid Interface Sci. 2007 Oct 1;314(1):281-8. PubMed, CrossRef
  29. Nikolaev IV, Lebedev VT, Grushko YuS, Sedov VP, Shilin VA, Török Gy, Melenevskaya EYu. Ordering of hydroxylated fullerenes in aqueous solutions. Fuller Nanotub Carbon Nanostruct. 2012;2(4-7):345-50. CrossRef
  30. Cleland WW. The kinetics of enzyme-catalyzed reactions with two or more substrates or products. II. Inhibition: nomenclature and theory. Biochim Biophys Acta. 1963 Feb 12;67:173-87. PubMed, CrossRef
  31. Fromm HJ. Use of competitive inhibitors to study substrate binding order. Methods Enzymol. 1979;63:467-86. PubMed, CrossRef
  32. Wiesmann C, Barr KJ, Kung J, Zhu J, Erlanson DA, Shen W, Fahr BJ, Zhong M, Taylor L, Randal M, McDowell RS, Hansen SK. Allosteric inhibition of protein tyrosine phosphatase 1B. Nat Struct Mol Biol. 2004 Aug;11(8):730-7. PubMed
  33. Olmez EO, Alakent B. Alpha7 helix plays an important role in the conformational stability of PTP1B. J Biomol Struct Dyn. 2011 Apr;28(5):675-93. PubMed, CrossRef
  34. Kamerlin SC, Rucker R, Boresch S. A targeted molecular dynamics study of WPD loop movement in PTP1B. Biochem Biophys Res Commun. 2006 Jul 7;345(3):1161-6. PubMed, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.