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)
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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.
KeywordsBuffer composition Capillary electrophoresis Cisplatin DNA binding Nucleotides Mass spectrometry
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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