Analysis of platinum adducts with DNA nucleotides and nucleosides by capillary electrophoresis coupled to ESI-MS: Indications of guanosine 5'-monophosphate O6-N7 chelation
- Author(s)
- Ulrich Warnke, Christina Rappel, Heiko Meier, Charlotte Kloft, Mathea Sophia Galanski, Christian Hartinger, Bernhard Keppler, Ulrich Jaehde
- Abstract
DNA is the ultimate target of platinum-based anticancer therapy. Since the N7 of guanine is known to be the major binding site of cisplatin and its analogues, adduct formation with model nucleotides, especially 2'-deoxyguanosine 5'-monophosphate (dGMP), has been studied in detail. During the last few years a coupled capillary eletrophoresis/ electrospray-ionization mass spectrometry (CE/ESI-MS) method has been advantageously used in order to separate and identify platinum adducts with nucleotides in submillimolar concentrations in aqueous solutions. Beside the bis-adduct, [Pt(NH3)2(dNMP)2]2- (NMP = 2'-deoxynucleoside 5'-monophosphate), and the well-known monochloro and monohydroxo adducts, [Pt(NH3)2Cl(dNMP)] - and [Pt(NH3)2(dNMP)OH]-, respectively, a third kind of monoadduct species with a composition of [Pt(NH3)2(dNMP)]- can be separated by CE and detected through the m/z values measured with ESI-MS. Different experimental setups indicate the existence of an O6-N7 chelate, whereas the formation of W-aPO4 macrochelates or dinuclear species is unlikely. Additionally, offline MS experiments with 2'-deoxyguanosine (dG) and stabilization of the controversially discussed O6-N7 chelate by oxidation with hydrogen peroxide support the assumption of the existence of O6-N7 chelation.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Freie Universität Berlin (FU), Universität Münster, Rheinische Friedrich-Wilhelms-Universität Bonn
- Journal
- ChemBioChem: a european journal of chemical biology
- Volume
- 5
- Pages
- 1543-1549
- No. of pages
- 7
- ISSN
- 1439-4227
- Publication date
- 2004
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 1040 Chemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/19023da5-3af6-4264-922f-a835860ac3a1