Spectral Study on the Interactions Among Cu(II), Doxorubicin and CopC

  • Yunxi Song
  • Zhen Song
  • Binsheng Yang


Interactions among Cu(II), doxorubicin and CopC have been investigated in detail by means of fluorescence, UV-Vis, IR spectra, isothermal titration calorimetry(ITC) and molecular docking in Tris-HCl buffer(50 mmol/L, pH=7.4, 25 °C). The results suggest that Cu(II)-doxorubicin is formed in a Cu(II) to doxorubicin ratio of 1:2, and the conditional stability constant, K[Cu(II)-doxorubicin] is 1.90×109 L2/mol2, CopC and doxorubicin can form a 1:1 complex, the conditional stability constant is greater than 105 L/mol. Binding of doxorubicin causes a conformational change in CopC with the reduction of β-sheet and increase of random coil, and the stability of CopC is decreased. Cu(II), doxorubicin and CopC can form a CopC-Cu(II)-doxorubicin ternary complex. The formation of CopC-Cu(II)- doxorubicin reduced greatly the reduction rate of Cu(II) by ascorbate(Vc), i.e. the binding of doxorubicin affects the action of CopC as redox switch.


Doxorubicin CopC Cu(II) Interaction 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



Thanks to Large-scale Scientific Instrument Center of Shanxi University for the use of Isothermal Titration Calorimetry 200.

Supplementary material

40242_2019_8284_MOESM1_ESM.pdf (512 kb)
Spectral study on the interaction between doxorubicin and CopC


  1. [1]
    Mandinov L., Mandinova A., Kyurkchiev S., Kyurkchiev D., Kehayov I., Kolev V., Soldi R., Bagala C., de Muinck E. D., Lindner V., Proc. Natl. Acad. Sci., 2003, 100(11), 6700CrossRefGoogle Scholar
  2. [2]
    Wang J., Luo C., Shan C., You Q., Lu J., Elf S., Zhou Y., Wen Y., Vinkenborg J. L., Fan J., Kang H., Lin R., Han D., Xie Y., Karpus J., Chen S., Ouyang S., Luan C., Zhang N., Ding H., Merkx M., Liu H., Chen J., Jiang H., He C., Nat. Chem., 2015, 7(12), 968CrossRefGoogle Scholar
  3. [3]
    Eatock M. M., Schätzlein A., Kaye S. B., Cancer Treat. Rev., 2000, 26(3), 191CrossRefGoogle Scholar
  4. [4]
    Lowndes S. A., Harris A. L., J. Mammary Gland Biol., 2005, 10(4), 299CrossRefGoogle Scholar
  5. [5]
    Rae T. D., Schmidt P. J., Pufahl R. A., Culotta V. C., O’Halloran T. V., Science, 1999, 284(5415), 805CrossRefGoogle Scholar
  6. [6]
    Puig S., Thiele D. J., Curr. Opin. Chem. Biol., 2002, 6(2), 171CrossRefGoogle Scholar
  7. [7]
    O’Halloran T. V., Culotta V. C., Metallochaperones, J. Biol. Chem., 2000, 275(33), 25057CrossRefGoogle Scholar
  8. [8]
    Finney L. A., O’Halloran T. V., Science, 2003, 300(5621), 931CrossRefGoogle Scholar
  9. [9]
    Robinson N. J., Winge D. R., Annu. Rev. Biochem., 2010, 79(1), 537CrossRefGoogle Scholar
  10. [10]
    Arnesano F., Banci L., Bertini I., Thompsett A. R., Structure, 2002, 10(10), 1337CrossRefGoogle Scholar
  11. [11]
    Djoko K. Y., Xiao Z., Huffman D. L., Wedd A. G., Inorg. Chem., 2007, 46(11), 4560CrossRefGoogle Scholar
  12. [12]
    Arnesano F., Banci L., Bertini I., Mangani S., Thompsett A. R., Proc. Natl. Acad. Sci., 2003, 100(7), 3814CrossRefGoogle Scholar
  13. [13]
    Koay M., Zhang L., Yang B. S., Maher M. J., Xiao Z. G., Wedd A. G., Inorg. Chem., 2005, 44(15), 5203CrossRefGoogle Scholar
  14. [14]
    Song Z., Zheng X. Y., Yang B. S., Protein Sci., 2013, 22(11), 1519CrossRefGoogle Scholar
  15. [15]
    Song Z., Ming J., Yang B. S., J. Biol. Inorg. Chem., 2014, 19(3), 359CrossRefGoogle Scholar
  16. [16]
    Sze C. M., Khairallah G. N., Xiao Z. G., Donnelly P. S., O’Hair R. A. J., Wedd A. G., J. Biol. Inorg. Chem., 2009, 14(2), 163CrossRefGoogle Scholar
  17. [17]
    Pang E. G., Zhao Y. Q., Yang B. S., Chin. Sci. Bull., 2005, 50(20), 2302CrossRefGoogle Scholar
  18. [18]
    Song Z., Wang J. L., Yang B. S., Spectrochim. Acta, Part A, 2014, 118, 454CrossRefGoogle Scholar
  19. [19]
    Song Z., Yuan W., Zhu R. T., Wang S., Zhang C. F., Int. J. Biol. Macromol., 2017, 96, 192CrossRefGoogle Scholar
  20. [20]
    Ren X. L., Song Z., Yang B. S., Chinese J. Inorg. Chem., 2015, 31(9), 1811Google Scholar
  21. [21]
    Hosseini Moltlagh N. S., Parvin P., Refahizadeh M., Bavali A., Appl. Opt., 2017, 56(26), 7498Google Scholar
  22. [22]
    Thao L. Q., Byeon H. J., Lee C., Lee E. S., Choi Y. W., Choi H. G., Park E. S., Lee K. C., Youn Y. S., Pharm. Res., 2016, 33(3), 615CrossRefGoogle Scholar
  23. [23]
    Dreis S., Rothweiler F., Michaelis M., Cinatl J., Langer K., Kreuter J., Int. J. Pharmaceut., 2007, 34(1), 207CrossRefGoogle Scholar
  24. [24]
    Byler D. M., Susi H., Biopolymers, 1986, 25(3), 469CrossRefGoogle Scholar
  25. [25]
    Mandeville J. S., Froehlich E., Tajmir-Riahi H. A., J. Pharm. Biomed., 2009, 49(2), 468CrossRefGoogle Scholar
  26. [26]
    Alam P., Chaturvedi S. K., Anwar T., Siddiqi M. K., Ajmal M. R., Badr G., Mahmoud M. H., Khan R. H., J. Lumin., 2015, 164, 123CrossRefGoogle Scholar
  27. [27]
    Möhler J. S., Kolmar T., Synnatschke K., Hergert M., Wilson L. A., Ramu S., Elliott A. G., Blaskovich M. T., Sidjabat H. E., Paterson D. L., J. Inorg. Biochem., 2017, 167, 134CrossRefGoogle Scholar
  28. [28]
    Kantonen S. A., Henriksen N. M., Gilson M. K., Biochim. Biophys. Acta, 2017, 1861(2), 485CrossRefGoogle Scholar
  29. [29]
    Johnson R. A., Manley O. M., Spuches A. M., Grossoehme N. E., Biochim. Biophys. Acta, 2016, 1860(5), 892CrossRefGoogle Scholar
  30. [30]
    Shi E. X., Zhang W. L., Zhao Y. Q., Yang B. S., RSC Adv., 2017, 7, 27139CrossRefGoogle Scholar
  31. [31]
    Yang B. S., Song Z., Zheng X. Y., Zhao Y. Q., Science China Chemistry, 2012, 55(7), 1351CrossRefGoogle Scholar

Copyright information

© Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular ScienceShanxi UniversityTaiyuanP. R. China
  2. 2.Department of ChemistryTaiyuan Normal UniversityJinzhongP. R. China

Personalised recommendations