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Sensitivity enhancement of homonuclear multidimensional NMR correlations for labile sites in proteins, polysaccharides, and nucleic acids

Multidimensional TOCSY and NOESY are central experiments in chemical and biophysical NMR. Limited efficiencies are an intrinsic downside of these methods, particularly when targeting labile sites. This study demonstrates that the decoherence imparted on these protons through solvent exchanges can, w...

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Autores principales: Novakovic, Mihajlo, Kupče, Ēriks, Oxenfarth, Andreas, Battistel, Marcos D., Freedberg, Darón I., Schwalbe, Harald, Frydman, Lucio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577996/
https://www.ncbi.nlm.nih.gov/pubmed/33087707
http://dx.doi.org/10.1038/s41467-020-19108-x
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author Novakovic, Mihajlo
Kupče, Ēriks
Oxenfarth, Andreas
Battistel, Marcos D.
Freedberg, Darón I.
Schwalbe, Harald
Frydman, Lucio
author_facet Novakovic, Mihajlo
Kupče, Ēriks
Oxenfarth, Andreas
Battistel, Marcos D.
Freedberg, Darón I.
Schwalbe, Harald
Frydman, Lucio
author_sort Novakovic, Mihajlo
collection PubMed
description Multidimensional TOCSY and NOESY are central experiments in chemical and biophysical NMR. Limited efficiencies are an intrinsic downside of these methods, particularly when targeting labile sites. This study demonstrates that the decoherence imparted on these protons through solvent exchanges can, when suitably manipulated, lead to dramatic sensitivity gains per unit time in the acquisition of these experiments. To achieve this, a priori selected frequencies are encoded according to Hadamard recipes, while concurrently subject to looped selective inversion or selective saturation procedures. Suitable processing then leads to protein, oligosaccharide and nucleic acid cross-peak enhancements of ≈200–1000% per scan, in measurements that are ≈10-fold faster than conventional counterparts. The extent of these gains will depend on the solvent exchange and relaxation rates of the targeted sites; these gains also benefit considerably from the spectral resolution provided by ultrahigh fields, as corroborated by NMR experiments at 600 MHz and 1 GHz. The mechanisms underlying these experiments’ enhanced efficiencies are analyzed on the basis of three-way polarization transfer interplays between the water, labile and non-labile protons, and the experimental results are rationalized using both analytical and numerical derivations. Limitations as well as further extensions of the proposed methods, are also discussed.
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spelling pubmed-75779962020-10-29 Sensitivity enhancement of homonuclear multidimensional NMR correlations for labile sites in proteins, polysaccharides, and nucleic acids Novakovic, Mihajlo Kupče, Ēriks Oxenfarth, Andreas Battistel, Marcos D. Freedberg, Darón I. Schwalbe, Harald Frydman, Lucio Nat Commun Article Multidimensional TOCSY and NOESY are central experiments in chemical and biophysical NMR. Limited efficiencies are an intrinsic downside of these methods, particularly when targeting labile sites. This study demonstrates that the decoherence imparted on these protons through solvent exchanges can, when suitably manipulated, lead to dramatic sensitivity gains per unit time in the acquisition of these experiments. To achieve this, a priori selected frequencies are encoded according to Hadamard recipes, while concurrently subject to looped selective inversion or selective saturation procedures. Suitable processing then leads to protein, oligosaccharide and nucleic acid cross-peak enhancements of ≈200–1000% per scan, in measurements that are ≈10-fold faster than conventional counterparts. The extent of these gains will depend on the solvent exchange and relaxation rates of the targeted sites; these gains also benefit considerably from the spectral resolution provided by ultrahigh fields, as corroborated by NMR experiments at 600 MHz and 1 GHz. The mechanisms underlying these experiments’ enhanced efficiencies are analyzed on the basis of three-way polarization transfer interplays between the water, labile and non-labile protons, and the experimental results are rationalized using both analytical and numerical derivations. Limitations as well as further extensions of the proposed methods, are also discussed. Nature Publishing Group UK 2020-10-21 /pmc/articles/PMC7577996/ /pubmed/33087707 http://dx.doi.org/10.1038/s41467-020-19108-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Novakovic, Mihajlo
Kupče, Ēriks
Oxenfarth, Andreas
Battistel, Marcos D.
Freedberg, Darón I.
Schwalbe, Harald
Frydman, Lucio
Sensitivity enhancement of homonuclear multidimensional NMR correlations for labile sites in proteins, polysaccharides, and nucleic acids
title Sensitivity enhancement of homonuclear multidimensional NMR correlations for labile sites in proteins, polysaccharides, and nucleic acids
title_full Sensitivity enhancement of homonuclear multidimensional NMR correlations for labile sites in proteins, polysaccharides, and nucleic acids
title_fullStr Sensitivity enhancement of homonuclear multidimensional NMR correlations for labile sites in proteins, polysaccharides, and nucleic acids
title_full_unstemmed Sensitivity enhancement of homonuclear multidimensional NMR correlations for labile sites in proteins, polysaccharides, and nucleic acids
title_short Sensitivity enhancement of homonuclear multidimensional NMR correlations for labile sites in proteins, polysaccharides, and nucleic acids
title_sort sensitivity enhancement of homonuclear multidimensional nmr correlations for labile sites in proteins, polysaccharides, and nucleic acids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577996/
https://www.ncbi.nlm.nih.gov/pubmed/33087707
http://dx.doi.org/10.1038/s41467-020-19108-x
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