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DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions

G-quadruplex DNA structures have become attractive drug targets, and native mass spectrometry can provide detailed characterization of drug binding stoichiometry and affinity, potentially at high throughput. However, the G-quadruplex DNA polymorphism poses problems for interpreting ligand screening...

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Detalles Bibliográficos
Autores principales: Ghosh, Anirban, Largy, Eric, Gabelica, Valérie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913678/
https://www.ncbi.nlm.nih.gov/pubmed/33555347
http://dx.doi.org/10.1093/nar/gkab039
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author Ghosh, Anirban
Largy, Eric
Gabelica, Valérie
author_facet Ghosh, Anirban
Largy, Eric
Gabelica, Valérie
author_sort Ghosh, Anirban
collection PubMed
description G-quadruplex DNA structures have become attractive drug targets, and native mass spectrometry can provide detailed characterization of drug binding stoichiometry and affinity, potentially at high throughput. However, the G-quadruplex DNA polymorphism poses problems for interpreting ligand screening assays. In order to establish standardized MS-based screening assays, we studied 28 sequences with documented NMR structures in (usually ∼100 mM) potassium, and report here their circular dichroism (CD), melting temperature (T(m)), NMR spectra and electrospray mass spectra in 1 mM KCl/100 mM trimethylammonium acetate. Based on these results, we make a short-list of sequences that adopt the same structure in the MS assay as reported by NMR, and provide recommendations on using them for MS-based assays. We also built an R-based open-source application to build and consult a database, wherein further sequences can be incorporated in the future. The application handles automatically most of the data processing, and allows generating custom figures and reports. The database is included in the g4dbr package (https://github.com/EricLarG4/g4dbr) and can be explored online (https://ericlarg4.github.io/G4_database.html).
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spelling pubmed-79136782021-03-03 DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions Ghosh, Anirban Largy, Eric Gabelica, Valérie Nucleic Acids Res Structural Biology G-quadruplex DNA structures have become attractive drug targets, and native mass spectrometry can provide detailed characterization of drug binding stoichiometry and affinity, potentially at high throughput. However, the G-quadruplex DNA polymorphism poses problems for interpreting ligand screening assays. In order to establish standardized MS-based screening assays, we studied 28 sequences with documented NMR structures in (usually ∼100 mM) potassium, and report here their circular dichroism (CD), melting temperature (T(m)), NMR spectra and electrospray mass spectra in 1 mM KCl/100 mM trimethylammonium acetate. Based on these results, we make a short-list of sequences that adopt the same structure in the MS assay as reported by NMR, and provide recommendations on using them for MS-based assays. We also built an R-based open-source application to build and consult a database, wherein further sequences can be incorporated in the future. The application handles automatically most of the data processing, and allows generating custom figures and reports. The database is included in the g4dbr package (https://github.com/EricLarG4/g4dbr) and can be explored online (https://ericlarg4.github.io/G4_database.html). Oxford University Press 2021-02-08 /pmc/articles/PMC7913678/ /pubmed/33555347 http://dx.doi.org/10.1093/nar/gkab039 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structural Biology
Ghosh, Anirban
Largy, Eric
Gabelica, Valérie
DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions
title DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions
title_full DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions
title_fullStr DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions
title_full_unstemmed DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions
title_short DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions
title_sort dna g-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913678/
https://www.ncbi.nlm.nih.gov/pubmed/33555347
http://dx.doi.org/10.1093/nar/gkab039
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