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The interaction of platinum-based drugs with native biologically relevant proteins

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Abstract

This study focuses on the identification of the products that are formed upon binding of therapeutically relevant platinum complexes to proteins like β-lactoglobulin A (LGA), human serum albumin (HSA), or human hemoglobin (HB). The respective proteins were incubated with the platinum-based anticancer drugs cisplatin, carboplatin, and oxaliplatin. LGA was selected as the model protein in addition to the two most abundant blood proteins HSA and HB. In case of the model protein, the effect of free thiol groups on the affinity of cisplatin, carboplatin, and oxaliplatin was investigated by means of liquid chromatography electrospray ionization time-of-flight mass spectrometry (LC/ESI-ToF-MS). The reduced form of LGA, which contains four free thiol groups more than the native LGA, shows a much higher affinity to the platinum-based drugs. By means of liquid chromatography coupled to inductively coupled plasma mass spectrometry, the reaction behavior of the platinum-based drugs towards HSA and HB was investigated under different conditions considering the chloride concentration (4 or 100 mM) and the incubation time (24 and 48 h). In case of carboplatin, less than 6 % protein-bound platinum was detected. However, both cisplatin and oxaliplatin display a high affinity to the proteins investigated. Further information was obtained by means of LC/ESI-ToF-MS. In case of oxaliplatin, the complex [Pt(DACH)]2+ (DACH = C6N2H14) was identified interacting with HSA and HB. For cisplatin, different results were observed for the two proteins. The complex [Pt(NH3)2Cl]+ interacted predominantly with HSA and [Pt(NH3)2]2+ with HB.

 

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Authors and Affiliations

  1. Institute of Inorganic and Analytical Chemistry, University of Münster, Corrensstr. 28/30, 48149, Münster, Germany

    Christine Brauckmann, Christoph A. Wehe, Michael Kieshauer, Michael Sperling & Uwe Karst

  2. Department of Paediatric Haematology and Oncology, University Children’s Hospital, Albert-Schweitzer Campus 1 A1, 48149, Münster, Germany

    Claudia Lanvers-Kaminsky

  3. European Virtual Institute for Speciation Analysis (EVISA), Mendelstr.11, 48149, Münster, Germany

    Michael Sperling

Authors
  1. Christine Brauckmann
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  2. Christoph A. Wehe
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  3. Michael Kieshauer
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  4. Claudia Lanvers-Kaminsky
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  5. Michael Sperling
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  6. Uwe Karst
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Correspondence to Uwe Karst.

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Published in the topical collection Metallomics with guest editors Uwe Karst and Michael Sperling

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Brauckmann, C., Wehe, C.A., Kieshauer, M. et al. The interaction of platinum-based drugs with native biologically relevant proteins. Anal Bioanal Chem 405, 1855–1864 (2013). https://doi.org/10.1007/s00216-012-6410-z

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  • DOI: https://doi.org/10.1007/s00216-012-6410-z

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