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

Abstract

The combination of proton detection with cryogenic dynamic nuclear polarization (DNP) promises to unite the intrinsic sensitivity and resolution of 1 H‐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 13 CHD 2 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 1 H‐ 1 H 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.

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BibTeX

@article{tolchard2026preserving,
  title = {{Preserving Proton Resolution Under Cryogenic Dynamic Nuclear Polarization for Biomolecular Solid‐State NMR}},
  author = {James Tolchard and Tanguy Le Marchand and Nadia El Mammeri and Kshama Sharma and Ajit Kumar Bishoyi and Mélanie Berbon and Kristaps Jaudzems and Dorothea Wisser and Asen Daskalov and Sven Saupe and Jan Stanek and Zhiyu Sun and Olivier Ouari and Birgit Habenstein and Anne Lesage and Guido Pintacuda and Antoine Loquet},
  journal = {Angewandte Chemie International Edition},
  year = {2026},
  month = aug,
  doi = {10.1002/anie.3761769},
  url = {https://u-bordeaux.hal.science/hal-05745829v1},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Preserving Proton Resolution Under Cryogenic Dynamic Nuclear Polarization for Biomolecular Solid‐State NMR
AU  - James Tolchard
AU  - Tanguy Le Marchand
AU  - Nadia El Mammeri
AU  - Kshama Sharma
AU  - Ajit Kumar Bishoyi
AU  - Mélanie Berbon
AU  - Kristaps Jaudzems
AU  - Dorothea Wisser
AU  - Asen Daskalov
AU  - Sven Saupe
AU  - Jan Stanek
AU  - Zhiyu Sun
AU  - Olivier Ouari
AU  - Birgit Habenstein
AU  - Anne Lesage
AU  - Guido Pintacuda
AU  - Antoine Loquet
PY  - 2026
DA  - 2026/08/26
JO  - Angewandte Chemie International Edition
DO  - 10.1002/anie.3761769
UR  - https://u-bordeaux.hal.science/hal-05745829v1
AB  - The combination of proton detection with cryogenic dynamic nuclear polarization (DNP) promises to unite the intrinsic sensitivity and resolution of 1 H‐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 13 CHD 2 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 1 H‐ 1 H 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.
SN  - 1433-7851
SN  - 1521-3773
ER  -

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