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:
- Oberacher, H., Pitterl, F., Plattner, S., Erb, R.
Mass Spectrometric Methods for Monitoring Processes in Electrochemical Cells
Mass Spectrometry Reviews, 34 (2015), 64-92.
- 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.
- 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.
- 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.
Austrian Science Fund (FWF): Simulation of redox processes involving nucleic acids, Project P 22526-B11, 2010-2013.