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

• Published in: Nature communications Vol. 11; no. 1; p. 5317
• Main Authors: Novakovic, Mihajlo, Kupče, Ēriks, Oxenfarth, Andreas, Battistel, Marcos D., Freedberg, Darón I., Schwalbe, Harald, Frydman, Lucio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21-10-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 101/6; 140/131; 631/45/535; 631/535/878/1263; 639/638/440/56; Data acquisition; Exchanging; Experiments; Humanities and Social Sciences; multidisciplinary; Multiplexing; NMR; Nuclear magnetic resonance; Nucleic acids; Oligosaccharides; Polysaccharides; Proteins; Protons; Saccharides; Science; Science (multidisciplinary); Sensitivity enhancement; Solvents; Spectral resolution
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19108-x

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.
Here, the authors present an approach that enhances the sensitivity of basic 2D biomolecular NMR experiments like NOESY and TOCSY, when carried out in polysaccharides, proteins and nucleic acids. This method combines principles associated to quantum Anti-Zeno Effects and advanced data acquisition methods based on Hadamard multiplexing.