Direct determination of the binding sites of cisplatin on insulin-like growth factor-1 by top-down mass spectrometry
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  • 作者:Ningbo Zhang (1) (2)
    Huan Liu (1) (2)
    Meng Cui (1)
    Yonggang Du (1) (2)
    Zhiqiang Liu (1)
    Shuying Liu (1)
  • 关键词:Insulin ; like growth factor ; 1 ; Anticancer drug ; Top鈥揹own ; Mass spectrometry
  • 刊名:Journal of Biological Inorganic Chemistry
  • 出版年:2015
  • 出版时间:January 2015
  • 年:2015
  • 卷:20
  • 期:1
  • 页码:1-10
  • 全文大小:566 KB
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  • 作者单位:Ningbo Zhang (1) (2)
    Huan Liu (1) (2)
    Meng Cui (1)
    Yonggang Du (1) (2)
    Zhiqiang Liu (1)
    Shuying Liu (1)

    1. Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People鈥檚 Republic of China
    2. University of the Chinese Academy of Sciences, Beijing, 100049, People鈥檚 Republic of China
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Life Sciences
    Biochemistry
    Microbiology
  • 出版者:Springer Berlin / Heidelberg
  • ISSN:1432-1327
文摘
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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