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Direct determination of the binding sites of cisplatin on insulin-like growth factor-1 by top-down mass spectrometry

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Abstract

Cisplatin has been widely used in the chemotherapy of a variety of tumors, and the interactions of cisplatin with proteins play very important roles in its side effects and drug resistance, as well as its pharmacokinetics and the biodistribution. Insulin-like growth factor-1 (IGF-1) was found to be associated with the drug resistance of cisplatin. Here, the interaction between cisplatin and IGF-1 was investigated using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. IGF-1-Pt(NH3)Cl was the main mono-adduct and the trans labilization was important to the reaction between IGF-1 and cisplatin, while another special mono-adduct IGF-1-Pt(NH3)Cl2 was observed. The rapid and sensitive top-down mass spectrometry-based approach in linear ion trap mass spectrometer has been developed to identify the binding sites of cisplatin in IGF-1 directly without tedious enzyme digestion. Three binding sites (Met59, Arg56 and Cys6) of cisplatin in IGF-1 were determined. The results not only provide a rapid and efficient way to identify the platinum binding sites in proteins, but also indicate that the binding of cisplatin could promote the fragmentation of IGF-1 and the rupture of disulfide bond.

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Acknowledgments

This work was financially supported by National Natural Science Foundation of China (No. 21103160) and Science and Technology Development Project of Jilin Province (No. 201105032).

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Authors and Affiliations

  1. Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People’s Republic of China

    Ningbo Zhang, Huan Liu, Meng Cui, Yonggang Du, Zhiqiang Liu & Shuying Liu

  2. University of the Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China

    Ningbo Zhang, Huan Liu & Yonggang Du

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  1. Ningbo Zhang
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  2. Huan Liu
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  3. Meng Cui
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  4. Yonggang Du
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  5. Zhiqiang Liu
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  6. Shuying Liu
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Correspondence to Meng Cui.

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Zhang, N., Liu, H., Cui, M. et al. Direct determination of the binding sites of cisplatin on insulin-like growth factor-1 by top-down mass spectrometry. J Biol Inorg Chem 20, 1–10 (2015). https://doi.org/10.1007/s00775-014-1202-x

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  • DOI: https://doi.org/10.1007/s00775-014-1202-x

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