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Mass spectrometric studies on the interaction of cisplatin and insulin

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Abstract

The interaction of antitumor drug, cisplatin (cis-[PtCl2(NH3)2], CDDP) with insulin from porcine pancreas has been investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and high resolution hybrid ion trap/time-of-flight mass spectrometry (MALIDI-TOF/TOF–MS and ESI-IT/TOF MS). The MALDI-TOF/TOF–MS results demonstrated that the presence of cisplatin complex resulted in the reduction of the disulfide bond in porcine pancreas after the incubations of the two substances were performed in vitro. It indicated that the presence of cisplatin would destroy the native configuration of insulin, which may lead to the inactivation of insulin. High resolution mass values and the characteristic isotopic pattern of the platinated insulin ions allowed the analysis of platinated mono-, di- and triadducts of cisplatin and insulin in the incubations under different conditions. The laser-induced dissociation of the monoadduct obtained in MALDI source was carried out and one platinum was found to bind to insulin B chain was determined. The platinum binding sites were further identified to be the N terminus (B chain), cysteine 7 (B chain) and cysteine 19 (B chain) residues by electrospray ionization tandem mass spectrometry. The identification of the interaction between insulin and cisplatin broadens the horizon of the knowledge in the interaction of the proteins and metallodrugs.

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Acknowledgments

The authors gratefully acknowledge the financial support from the National Science Foundation of China (Nos: 20327010 and 21532005) and Hi-Tech Research and Development Program of China (863 Program, No. 2010AA101502).

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Authors and Affiliations

  1. Department of Chemical and Biological Engineering, Institute of Biological Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang, China

    Jing Li & Lirong Yang

  2. Department of Chemistry, Zhejiang University, Hangzhou, 310027, Zhejiang, China

    Jing Li, Lei Yue, Yaqin Liu, Xinchi Yin, Qi Yin & Yuanjiang Pan

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  1. Jing Li
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  2. Lei Yue
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  3. Yaqin Liu
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  7. Lirong Yang
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Correspondence to Yuanjiang Pan or Lirong Yang.

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Handling Editor: K. L. Bennett.

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Li, J., Yue, L., Liu, Y. et al. Mass spectrometric studies on the interaction of cisplatin and insulin. Amino Acids 48, 1033–1043 (2016). https://doi.org/10.1007/s00726-015-2159-y

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  • DOI: https://doi.org/10.1007/s00726-015-2159-y

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