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Analysis of Platinum Adducts with DNA Nucleotides and Nucleosides by Capillary Electrophoresis Coupled to ESI‐MS: Indications of Guanosine 5′‐Monophosphate O 6 – N 7 Chelation
Author(s) -
Warnke Ulrich,
Rappel Christina,
Meier Heiko,
Kloft Charlotte,
Galanski Mathea Sophia,
Hartinger Christian G.,
Keppler Bernhard K.,
Jaehde Ulrich
Publication year - 2004
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400015
Subject(s) - guanosine , capillary electrophoresis , nucleotide , chemistry , adduct , chelation , platinum , dna , guanosine diphosphate , stereochemistry , platinum compounds , purine , guanine , biochemistry , chromatography , organic chemistry , enzyme , catalysis , gene
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 bisadduct, [Pt(NH 3 ) 2 (dNMP) 2 ] 2− (NMP=2′‐deoxynucleoside 5′‐monophosphate), and the well‐known monochloro and monohydroxo adducts, [Pt(NH 3 ) 2 Cl(dNMP)] − and [Pt(NH 3 ) 2 (dNMP)OH] − , respectively, a third kind of monoadduct species with a composition of [Pt(NH 3 ) 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 O 6 – N 7 chelate, whereas the formation of N 7– α PO 4 macrochelates or dinuclear species is unlikely. Additionally, offline MS experiments with 2′‐deoxyguanosine (dG) and stabilization of the controversially discussed O 6 – N 7 chelate by oxidation with hydrogen peroxide support the assumption of the existence of O 6 – N 7 chelation.