| Structures of oxaliplatin-oligonucleotide adducts from DNA. | |
MedLine Citation:
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PMID: 23019159 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Oxaliplatin, [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II) shows a great efficiency against colorectal cancer. Although the mode of action of oxaliplatin is not yet understood, it is commonly accepted that binding of oxaliplatin to DNA prevents DNA synthesis and alters protein to DNA binding. In order to elucidate the modified DNA-protein interaction and thus to understand the mechanisms leading to cellular misinterpretation of DNA information and apoptosis, we have identified the preferential binding sites and the dynamics of the oxaliplatin-DNA intrastrand and interstrand adducts at the oligomer level using high-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS) and HPLC/inductively coupled plasma-MS for quantitative studies. We used a combination of benzonase, alkaline phosphatase and Nuclease S1 for digestion. This digestion procedure allows the study of platinated oligomeric nucleotides and more complex interstrand adducts. The digestion products were mostly chromatographically separated and characterized using HPLC/ESI-ion trap MS/MS experiments. We could show that the adducts to guanine and adenine are quite dynamic; that is, the ratios are changing for several days. In addition, the resulting adducts provide evidence for the action of the digesting enzymes and indicate that the adduct spectrum at the oligomeric level is different to that at the commonly studies dinucleotide level. Copyright © 2012 John Wiley & Sons, Ltd. |
Authors:
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Shereen Mowaka; Matthias Ziehe; Dalia Mohamed; Ulrike Hochkirch; Jürgen Thomale; Michael W Linscheid |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of mass spectrometry : JMS Volume: 47 ISSN: 1096-9888 ISO Abbreviation: J Mass Spectrom Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-09-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9504818 Medline TA: J Mass Spectrom Country: England |
Other Details:
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Languages: eng Pagination: 1282-93 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 John Wiley & Sons, Ltd. |
Affiliation:
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Humboldt-Universitaet zu Berlin, Department of Chemistry, Berlin, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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