title: Direct determination of the binding sites of cisplatin on insulin-like growth factor-1 by top-down mass spectrometry.
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.
authors.affiliation: Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.|University of the Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
authors.forename: Ningbo
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.|University of the Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China. cuimeng@ciac.ac.cn.
authors.forename: Meng
authors.initials: M
authors.lastname: Cui
authors.affiliation: Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.|University of the Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Du
authors.affiliation: Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry*; D001665:Binding Sites; D002945:Cisplatin / Q000737:chemistry*; D005583:Fourier Analysis; D007334:Insulin-Like Growth Factor I / Q000737:chemistry*; D008969:Molecular Sequence Data; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D007334:Insulin-Like Growth Factor I; D002945:Cisplatin