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Characterization of nucleic acid higher order structure by high-resolution tandem mass spectrometry

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Abstract

Mass spectrometry (MS) is extensively used for the identification and sequencing of nucleic acids but has so far seen limited use for characterization of their higher order structures. Here, we have applied a range of different tandem mass spectrometry techniques, including electron detachment dissociation (EDD), infrared multiphoton dissociation (IRMPD), activated ion (AI) EDD, and EDD/IRMPD MS3, in a Fourier transform ion cyclotron resonance mass spectrometer to the characterization of three isomeric 15mer DNAs with different sequences and predicted solution-phase structures. Our goal was to explore whether their structural differences could be directly probed with these techniques. We found that all three 15mers had higher order structures in the gas phase, although preferred structures were predicted for only two of them in solution. Nevertheless, EDD, AI EDD, and EDD/IRMPD MS3 experiments yielded different cleavage patterns with less backbone fragmentation for the more stable solution-phase structure than for the other two 15mers. By contrast, no major differences were observed in IRMPD, although the extent of backbone cleavage was higher with that technique for all three 15mers. Thus, experiments utilizing the radical ion chemistry of EDD can provide complementary structural information compared to traditional slow heating methods, such as IRMPD, for structured nucleic acids.

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Acknowledgements

This work was supported by a research award from the American Society for Mass Spectrometry (sponsored by Thermo Electron), a starter grant from the Petroleum Research Fund, and an Elisabeth Caroline Crosby research award from the University of Michigan.

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Authors and Affiliations

  1. Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI, 48109-1055, USA

    Jingjie Mo & Kristina Håkansson

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  1. Jingjie Mo
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  2. Kristina Håkansson
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Correspondence to Kristina Håkansson.

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Mo, J., Håkansson, K. Characterization of nucleic acid higher order structure by high-resolution tandem mass spectrometry. Anal Bioanal Chem 386, 675–681 (2006). https://doi.org/10.1007/s00216-006-0614-z

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  • DOI: https://doi.org/10.1007/s00216-006-0614-z

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