Electrochemical simulation of oxidation reactions involving nucleic acids

DNA damage has important implications in human health and may be responsible for the development of different diseases including cancer. Oxidation represents a key step in the alteration of the genetic material responsible for mutagenesis, genotoxicity, and/or cancerogenesis. Oxidation reactions produce reactive electrophiles that covalently bind to nucleic acid molecules. One class of reactive electrophiles are reactive oxygen species (ROS); the other ones are (bio)activated small molecules.  

We have demonstrated that on-line electrochemistry (EC) - liquid chromatography (LC) - mass spectrometry (MS) is a convenient tool for testing the reactivity of synthetic nucleic acids with chemicals including tentative mutagenic compounds and ROS. EC is used to mimic oxidation processes; formed reaction products are separated by LC, which facilitates their consecutive detection and characterization with MS. Nucleic acids tested included nucleosides and nucleotides as well as small oligomers. Thus, EC/LC/MS is capable to study site-selectivity of reaction.  

By applying EC-LC-MS, we have gained new insights into the mechanisms guiding the reactivity between nucleic acids and (activated) molecules, and these have been summarized in the following publications:

  1. Oberacher, H.*, Pitterl, F., Plattner, S., Erb, R. Mass Spectrometric Methods for Monitoring Processes in Electrochemical Cells. Mass Spectrometry Reviews, 34 (2015), 64-92.
  2. Oberacher, H.*, Erb, R., Plattner, S., Chervet, J.-P. Mechanistic Aspects of Nucleic Acids Oxidation Studied with Electrochemistry-Mass Spectrometry. Trends in Analytical Chemistry, 70 (2015), 100-111.
  3. Erb, R., Plattner, S., Pitterl, F., Brouwer, H.-J., Oberacher, H.* An Optimized Electrochemistry-Liquid Chromatography-Mass Spectrometry Method for Studying Guanosine Oxidation. Electrophoresis, 33 (2012), 614-621.
  4. Pitterl, F., Chervet, J.-P., Oberacher, H.* Electrochemical Simulation of Oxidation Processes Involving Nucleic Acids Online Monitored with Electrospray Ionization-Mass Spectrometry. Analytical and Bioanalytical Chemistry, 397 (2010), 1203-1215.

Grant

Austrian Science Fund (FWF): Simulation of redox processes involving nucleic acids, Project P 22526-B11, 2010-2013.

Link

Antec Scientific

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