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Structural and Thermodynamic Investigation into the Protein-Binding Properties of a Natural Product Crytotanshinone

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Abstract

Crytotanshinone (CTSO) is a Chinese herbal medicine active ingredient isolated from Salvia miltiorrhiza. In this work, the interaction of CTSO and human serum albumin (HSA) was studied by fluorescence spectra, ultraviolet spectra, circular dichroism (CD) spectra, molecular probe and molecular modeling methods. The results showed that the endogenous fluorescence of HSA was quenched by CTSO through a static mechanism. The number of binding sites, equilibrium constants, and thermodynamic parameters of the reaction were calculated at three different temperatures. The positive enthalpy change (ΔHθ) and entropy change (ΔSθ) revealed that the interaction was an endothermic as well as an entropy-driven process, where hydrophobic power played the major role in stabilizing the structure of the new complex. Site-selective binding experiments were carried out using warfarin and ibuprofen as probes, which proved that CTSO binds to Sudlow’s site II in subdomain IIIA of the HSA molecule. Circular dichroism (CD) spectra was employed to detect the α-helix and β-strand contents in HSA before and after the binding of CTSO. Based on the experimental results, the structure of the CTSO–HSA complex was calculated by docking CTSO to the proven site using molecular modeling. The study obtained comprehensive information on structure and thermodynamics, which is essential for understanding the bioaffinity, delivery process and pharmacological mechanism.

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References

  1. Wang, B.-Q.: Salvia miltiorrhiza: chemical and pharmacological review of a medicinal plant. J. Med. Plants Res. 4, 2813–2820 (2010)

    CAS  Google Scholar 

  2. Fang, Z., Su, W., Zhang, W., Xu, Y., Xiong, Y., Luo, M., Fan, J., Yin, X.: Chiral discrimination and interaction mechanism between enantiomers and serum albumins. J. Mol. Recognit. 26, 161–164 (2013)

    Article  CAS  Google Scholar 

  3. Poureshghi, F., Ghandforoushan, P., Safarnejad, A., Soltani, S.: Interaction of an antiepileptic drug, lamotrigine with human serum albumin (HSA): application of spectroscopic techniques and molecular modeling methods. J. Photochem. Photobiol., B 166, 187–192 (2017)

    Article  CAS  Google Scholar 

  4. Bogdan, M., Floare, C.G., Pirnau, A., Neamtu, S.: Competitive binding of tolmetin to β-cyclodextrin and human serum albumin: 1H NMR and fluorescence spectroscopy studies. J. Solution Chem. 46, 44–57 (2017)

    Article  CAS  Google Scholar 

  5. Ariga, G.G., Naik, P.N., Nandibewoor, S.T., Chimatadar, S.A.: Study of fluorescence interaction and conformational changes of bovine serum albumin with histamine H1-receptor–drug epinastine hydrochloride by spectroscopic and time-resolved fluorescence methods. Biopolymers 103, 646–657 (2015)

    Article  CAS  Google Scholar 

  6. Kitagishi, H., Kawasaki, H., Kano, K.: Bioconjugation of serum albumin to a maleimide-appended porphyrin/cyclodextrin supramolecular complex as an artificial oxygen carrier in the bloodstream. Chem. Asian J. 10, 1768–1775 (2015)

    Article  CAS  Google Scholar 

  7. Carter, D.C., Ho, J.X.: Structure of serum albumin. Adv. Prot. Chem. 45, 153–203 (1994)

    Article  CAS  Google Scholar 

  8. Schneider, E.K., Huang, J.X., Carbone, V., Baker, M., Azad, M.A.K., Cooper, M.A., Li, J., Velkov, T.: Drug–drug plasma protein binding interactions of ivacaftor. J. Mol. Recognit. 28, 339–348 (2015)

    Article  CAS  Google Scholar 

  9. Chi, Z.X., Liu, R.T.: Phenotypic characterization of the binding of tetracycline to human serum albumin. Biomacromol. 12, 203–209 (2011)

    Article  CAS  Google Scholar 

  10. Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Olson, A.J.: AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30, 2785–2791 (2009)

    Article  CAS  Google Scholar 

  11. Kamat, B.P.: Study of the interaction between fluoroquinolones and bovine serum albumin. J. Pharm. Biomed. 39, 1046–1050 (2005)

    Article  CAS  Google Scholar 

  12. Hu, Y.J., Ou-Yang, Y., Dai, C.M., Liu, Y., Xiao, X.H.: Site-selective binding of human serum albumin by palmatine: spectroscopic approach. Biomacromol. 11, 106–112 (2010)

    Article  CAS  Google Scholar 

  13. Zhang, H.-X., Xiong, H.-X., Li, L.-W.: Investigation on the protein-binding properties of icotinib by spectroscopic and molecular modeling method. Spectrochim. Acta A 161, 88–94 (2016)

    Article  CAS  Google Scholar 

  14. Ali, M., Kumar, A., Kumar, M., Pandey, B.N.: The interaction of human serum albumin with selected lanthanide and actinide ions: binding affinities, protein unfolding and conformational changes. Biochimie 123, 117–129 (2016)

    Article  CAS  Google Scholar 

  15. Kandagal, P.B., Kalanur, S.S., Manjunatha, D.H., Seetharamappa, J.: Mechanism of interaction between human serum albumin and N-alkyl phenothiazines studied using spectroscopic methods. J. Pharm. Biomed. 47, 260–267 (2008)

    Article  CAS  Google Scholar 

  16. Zhang, Y.-Z., Zhou, B., Zhang, X.-P., Huang, P., Li, C.-H., Liu, Y.: Interaction of malachite green with bovine serum albumin: determination of the binding mechanism and binding site by spectroscopic methods. J. Hazard. Mater. 163, 1345–1352 (2009)

    Article  CAS  Google Scholar 

  17. Ross, P.D., Subramanian, S.: Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 20, 3096–3102 (1981)

    Article  CAS  Google Scholar 

  18. He, X.M., Carter, D.C.: Atomic structure and chemistry of human serum albumin. Nature 358, 209–215 (1992)

    Article  CAS  Google Scholar 

  19. Carter, D.C., He, X.M., Munson, S.H., Twigg, P.D., Gernert, K.M., Broom, M.B., Miller, T.Y.: Three-dimensional structure of human serum albumin. Science 244, 1195–1198 (1989)

    Article  CAS  Google Scholar 

  20. Zhang, H.-X., Zhang, Q., Wang, H.-L., Li, L.-W.: Comparison and analysis on the serum-binding characteristics of aspirin–zinc complex and aspirin. Luminescence 32, 1017–1024 (2017)

    Article  CAS  Google Scholar 

  21. Förster, T.: Intermolecular energy migration and fluorescence. Ann. Phys. 437, 55–75 (1948)

    Article  Google Scholar 

  22. Makarska-Bialokoz, M.: Investigation of the binding affinity in vitamin B12–bovine serum albumin system using various spectroscopic methods. Spectrochim. Acta A 184, 262–269 (2017)

    Article  CAS  Google Scholar 

  23. Zhang, H.-X., Liu, Y.: Protein-binding properties of a designed steroidal lactam compound. Steroids 80, 30–36 (2014)

    Article  CAS  Google Scholar 

  24. Cheng, H., Zou, T., Xu, Y., Wang, Y., Wu, A., Dai, J., Zhang, Y., Liu, Y.: Investigations on the interactions between naphthalimide-based anti-tumor drugs and human serum albumin by spectroscopic and molecular modeling methods. Luminescence 31, 88–95 (2016)

    Article  CAS  Google Scholar 

  25. Kumar, A., Ali, M., Ningthoujam, R.S., Gaikwad, P., Kumar, M., Nath, B.B., Pandey, B.N.: The interaction of actinide and lanthanide ions with hemoglobin and its relevance to human and environmental toxicology. J. Hazard. Mater. 307, 281–293 (2016)

    Article  CAS  Google Scholar 

  26. Yan, R., Lai, L., Xu, Z.-Q., Jiang, F.-L., Liu, Y.: Thermodynamics of the Interactions between quantum dots and proteins. Acta Phys. Chim. Sin. 33, 2377–2387 (2017)

    CAS  Google Scholar 

  27. Zhang, H.-X., Zhou, D., Xia, Q.H.: Study on the molecular recognition action of lamivudine by human serum albumin. J Mol Recognit. 31(7), e2705 (2018)

    Article  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the financial support by National Natural Science Foundation of China (21571055, 21673069 and 21503074),Research Foundation of Education Bureau of Hubei Province of China (D20184302, D20174301), and Jingmen Science and Technology Project (2018YFYB057).

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Authors and Affiliations

  1. Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Hubei University, Wuhan, Hubei, 430062, People’s Republic of China

    Hua-xin Zhang, Dan Zhou & Qing-hua Xia

  2. Hubei Key Laboratory of Drug Synthesis and Optimization, Jingchu University of Technology, Jingmen, Hubei, 448000, People’s Republic of China

    Hua-xin Zhang & E. Liu

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  1. Hua-xin Zhang
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  2. E. Liu
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  3. Dan Zhou
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  4. Qing-hua Xia
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Correspondence to Hua-xin Zhang or Dan Zhou.

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Zhang, Hx., Liu, E., Zhou, D. et al. Structural and Thermodynamic Investigation into the Protein-Binding Properties of a Natural Product Crytotanshinone. J Solution Chem 47, 2068–2081 (2018). https://doi.org/10.1007/s10953-018-0834-9

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  • DOI: https://doi.org/10.1007/s10953-018-0834-9

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