Preserving Proton Resolution Under Cryogenic Dynamic Nuclear Polarization for Biomolecular Solid-State NMR

Tolchard J, Le Marchand T, El Mammeri N, Sharma K, Bishoyi AK, Berbon M, Jaudzems K, Wisser D, Daskalov A, Saupe SJ, Stanek J, Sun Z, Ouari O, Habenstein B, Lesage A, Pintacuda G, Loquet A (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Angewandte Chemie International Edition Wiley

DOI: 10.1002/anie.3761769

Abstract

The combination of proton detection with cryogenic dynamic nuclear polarization (DNP) promises to unite the intrinsic sensitivity and resolution of 1H-detected magic-angle spinning (MAS) NMR with the large signal enhancements afforded by hyperpolarization, but has long been considered impractical because of cryogenic line broadening and the limited spinning frequencies available under DNP conditions. Here, we demonstrate that high-resolution proton-detected spectra of proteins can indeed be obtained under cryogenic DNP conditions. Using extensive deuteration, selective 13CHD2 methyl labeling, fast MAS and high magnetic fields, we show that site-resolved proton detection is preserved in both microcrystalline proteins and amyloid fibrils. Quantitative linewidth analysis reveals that, despite broader resonances, proton coherence lifetimes remain remarkably long because high magnetic fields, fast MAS, and extensive proton dilution efficiently suppress the homogeneous contribution, leaving the observed linewidth dominated by refocusable inhomogeneous broadening. The resulting sensitivity enables structurally informative proton-detected 1H-1H correlation spectroscopy under DNP conditions. These results establish proton-detected DNP as a practical methodology for biomolecular MAS NMR and extend structural studies to challenging protein assemblies limited by sensitivity, spectral crowding, or sample availability.

Involved external institutions

European Institute of Chemistry and Biology / Institut Européen de Chimie et Biologie (IECB) FR France (FR) École normale supérieure de Lyon (ENS) FR France (FR) Université de Bordeaux FR France (FR) Institute of Radical Chemistry / Institut de Chimie Radicalaire (ICR) FR France (FR)

How to cite

APA:

Tolchard, J., Le Marchand, T., El Mammeri, N., Sharma, K., Bishoyi, A.K., Berbon, M.,... Loquet, A. (2026). Preserving Proton Resolution Under Cryogenic Dynamic Nuclear Polarization for Biomolecular Solid-State NMR. Angewandte Chemie International Edition. https://doi.org/10.1002/anie.3761769

MLA:

Tolchard, James, et al. "Preserving Proton Resolution Under Cryogenic Dynamic Nuclear Polarization for Biomolecular Solid-State NMR." Angewandte Chemie International Edition (2026).

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