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Analytical and Bioanalytical Chemistry

, Volume 405, Issue 20, pp 6417–6424 | Cite as

A systematic capillary electrophoresis study on the effect of the buffer composition on the reactivity of the anticancer drug cisplatin to the DNA model 2′-deoxyguanosine 5′-monophosphate (dGMP)

  • Gerlinde Grabmann
  • Bernhard K. Keppler
  • Christian G. Hartinger
Research Paper

Abstract

The development of DNA-targeted next-generation platinum-based anticancer chemotherapeutics is often accompanied by studies on the reactivity to DNA models. However, the incubation conditions used in literature vary widely, and some of the buffer/salts used are known to form complexes with Pt. Such coordination can influence the binding process and also the adducts formed. In a systematic approach, studies on the binding of cisplatin (1 mM) to dGMP (2 mM) in a series of different incubation solutions of relevance to biological systems are reported, employing capillary zone electrophoresis (CZE) with UV/vis and electrospray ionization–mass spectrometric (ESI-MS) detectors. Kinetic experiments performed with CZE–UV showed a high reactivity of dGMP to cisplatin in pure water (τ 1/2 = 4.1 ± 0.7 h) but a significantly slowed down in a solution containing a carbonate/phosphate buffer supplemented with NaCl, resulting in a half-life of dGMP of 25 ± 3 h. Especially carbonate had a major impact on the binding, though no coordination to the metal center was detectable with the methods used. The only adducts containing buffer components were (phosphate)Pt and tris(ammine)Pt species, as identified by means of CZE–ESI-MS, in addition to the main adduct [Pt(NH3)2(dGMP)2 − 4H+]2− and other less abundant Pt-containing species.

Keywords

Buffer composition Capillary electrophoresis Cisplatin DNA binding Nucleotides Mass spectrometry 

Notes

Acknowledgments

We would like to thank the University of Vienna for a PhD scholarship for G.G. within the doctoral program BioProMoTION (Bioactivity Profiling and Metabolism) and COST CM1105 and the Austrian Science Fund (FWF, project number I496-B11) for financial support. Verena Pichler is acknowledged for preparing cisplatin, and G.G would like to thank Samuel M. Meier and Alexander E. Egger for fruitful discussions.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Gerlinde Grabmann
    • 1
  • Bernhard K. Keppler
    • 1
    • 2
  • Christian G. Hartinger
    • 1
    • 2
    • 3
  1. 1.Institute of Inorganic ChemistryUniversity of ViennaViennaAustria
  2. 2.Research Platform “Translational Cancer Therapy Research”University of ViennaViennaAustria
  3. 3.School of Chemical SciencesThe University of AucklandAucklandNew Zealand

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