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May the Best Molecule Win: Competition ESI Mass Spectrometry

Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA
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Academic Editor: Eric C. Long
Int. J. Mol. Sci. 2015, 16(10), 24506-24531; https://doi.org/10.3390/ijms161024506
Received: 28 August 2015 / Revised: 18 September 2015 / Accepted: 9 October 2015 / Published: 15 October 2015
(This article belongs to the Special Issue Low Molecular Weight DNA and RNA Binding Agents)
Electrospray ionization mass spectrometry has become invaluable in the characterization of macromolecular biological systems such as nucleic acids and proteins. Recent advances in the field of mass spectrometry and the soft conditions characteristic of electrospray ionization allow for the investigation of non-covalent interactions among large biomolecules and ligands. Modulation of genetic processes through the use of small molecule inhibitors with the DNA minor groove is gaining attention as a potential therapeutic approach. In this review, we discuss the development of a competition method using electrospray ionization mass spectrometry to probe the interactions of multiple DNA sequences with libraries of minor groove binding molecules. Such an approach acts as a high-throughput screening method to determine important information including the stoichiometry, binding mode, cooperativity, and relative binding affinity. In addition to small molecule-DNA complexes, we highlight other applications in which competition mass spectrometry has been used. A competitive approach to simultaneously investigate complex interactions promises to be a powerful tool in the discovery of small molecule inhibitors with high specificity and for specific, important DNA sequences. View Full-Text
Keywords: competition; mass spectrometry; electrospray; minor groove binder; DNA; transcription factor; specificity competition; mass spectrometry; electrospray; minor groove binder; DNA; transcription factor; specificity
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Laughlin, S.; Wilson, W.D. May the Best Molecule Win: Competition ESI Mass Spectrometry. Int. J. Mol. Sci. 2015, 16, 24506-24531.

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