Pushing the boundaries of NMR
Assistant Professor Thibault Viennet from iNANO and the Department of Chemistry has contributed to a Nature Chemistry paper, reporting on a novel nuclear magnetic resonance technology to investigate aromatic groups, even in very large molecules, which had not been possible to date.
NMR spectroscopy offers atomic-level insight into biomolecular structure, dynamics, and interactions. However, for large macromolecules (molecular mass greater than 35 kDa), rapid relaxation leads to line broadening and overlapping signals, limiting resolution and interpretability.
NMR spectroscopy offers atomic-level insight into biomolecular structure, dynamics, and interactions. However, for large macromolecular systems—typically those exceeding 35 kDa in molecular mass—rapid relaxation leads to severe line broadening and signal overlap, which limits spectral resolution and complicates data interpretation. To overcome these challenges, the team exploited the slow relaxation properties of ¹³C nuclei bonded to ¹⁹F in aromatic spin pairs, along with spin–spin coupling to meta-position protons, enabling the recording of high-resolution two-dimensional ¹H–¹³CF correlation spectra using transverse relaxation-optimized spectroscopy (TROSY) selection.
The team synthesized selectively isotope-labeled fluorophenylalanine engineered for optimal relaxation properties. They also established both residue-specific and site-specific incorporation strategies, enabling efficient integration of this novel amino acid into proteins.
This innovative approach resulted in narrow NMR linewidths in proteins ranging from 30 to 180 kDa, opening new possibilities for studying protein-ligand interactions without requiring specialized ¹⁹F probes—thus broadening the applicability of NMR to complex biomolecular systems.
The article, published in Nature Chemistry, has also been showcased in Nature Chemistry “News and Views” editorial.
About the study
Study type:
Experimental chemistry
External funding:
This work was based on research conducted at the Northeastern Collaborative Access Team beamlines, which were funded by the National Institute of General Medical Sciences from the National Institutes of Health (P30 GM124165). The Eiger 16M detector on the 24-ID-C beamline was funded by an NIH-ORIP HEI grant (S10OD021527). This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under contract number DE-AC02-06CH11357. S.D.-P. acknowledges funding from the Linde Family Foundation, the Doris Duke Charitable Foundation, Deerfield 3DC and Taiho Pharmaceuticals. V.V. acknowledges funding from the Brazilian National Council for Scientific and Technological Development CNPq grant 200611/2022-4. We acknowledge the generous support of the Austrian Science Fund (Erwin Schrödinger Fellowship FWF3872 awarded to A.B.), grants GM136859 and AI143565 awarded to H.A. and grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI grant number JP22K18374 (to K.T.), the Naito Foundation (to K.T.) and the Takeda Science Foundation (to K.T.). This work was supported in part by a gift from J. Goldberg, Dana-Farber Donor. This work was also supported in part by the GCE4All Biomedical Technology Optimization and Dissemination Center supported by the National Institute of General Medical Science grant RM1-GM144227. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the paper.
Conflicts of interest:
V.M.G. is the founder of FB Reagents Ltd., a company that provides isotopically enriched NMR reagents. C.A. works for Bruker BioSpin Corporation, which is a manufacturer of equipment used in this work. W.B. and H.K. were employees at Bruker BioSpin Corporation when this work was conducted and have since retired. H.A. is a co-founder of Quantum Therapeutics Inc., a company that employs computational methods for drug development, although the work presented here does not overlap with that of the company. The other authors declare no competing interests.
Link to the scientific article:
https://www.nature.com/articles/s41557-025-01818-8
Andras Boeszoermenyi, Denitsa L. Radeva, Sebastian Schindler, Veronica Valadares, Krishna M. Padmanabha Das, Abhinav Dubey, Thibault Viennet, Max Schmitt, Peter Kast, Vladimir M. Gelev, Nikolay Stoyanov, Nikola Burdzhiev, Ognyan Petrov, Scott Ficarro, Jarred Marto, Ezekiel A. Geffken, Sirano Dhe-Paganon, Hyuk-Soo Seo, Nathan D. Alexander, Richard B. Cooley, Ryan A. Mehl, Helena Kovacs, Clemens Anklin, Wolfgang Bermel, Ilya Kuprov, Koh Takeuchi, and Haribabu Arthanari
Contact information:
Tenure Track Assistant Professor Thibault Viennet
Aarhus University
Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry
Email: thibault@chem.au.dk