Assessment of Attainable Distances in Proteins by Through‐Space 19F–19F Couplings
- 1Department of Organic Chemistry I, Faculty of Chemistry University of the Basque Country (EHU) Donostia/San Sebastián Spain
- 2Department of Structural Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA
Abstract
19F NMR is becoming an increasingly powerful method for studying the conformation and ligand binding of proteins in the solid state and in solution. In liquids NMR, surprisingly, reports on through‐space 19F–19F coupling remain scarce. Here, we present the first 19F–19F NOESY study designed to calibrate inter‐fluorine distances in proteins. Three difluorinated tryptophan analogues (4,5‐F2‐Trp, 4,6‐F2‐Trp, 5,6‐F2‐Trp) were synthesized and site‐specifically incorporated into human cyclophilin A (CypA). Series of 19F–19F NOESY build‐up experiments were recorded for each labeled protein, and the extracted cross‐relaxation rates were compared to fixed reference distances. While small distances in the 2.5–3.0 Å range were easily accessible, the upper limit at 14.1 T is ∼5 Å. These results provide evidence that short distances can be extracted from 19F–19F NOESY spectra, expanding the toolbox for studying protein‐protein or protein‐ligand interactions by NMR.
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BibTeX
@article{hernandez2026assessment,
title = {{Assessment of Attainable Distances in Proteins by Through‐Space 19F–19F Couplings}},
author = {Iker Hernández and In‐Ja L. Byeon and Christina M. Monnie and Vadim A. Soloshonok and Aitor Landa and Mikel Oiarbide and Angela M. Gronenborn},
journal = {Chemistry (Weinheim an Der Bergstrasse, Germany)},
year = {2026},
month = jul,
doi = {10.1002/chem.71456},
url = {https://doi.org/10.1002/chem.71456},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Assessment of Attainable Distances in Proteins by Through‐Space 19F–19F Couplings
AU - Iker Hernández
AU - In‐Ja L. Byeon
AU - Christina M. Monnie
AU - Vadim A. Soloshonok
AU - Aitor Landa
AU - Mikel Oiarbide
AU - Angela M. Gronenborn
PY - 2026
DA - 2026/07/24
JO - Chemistry (Weinheim an Der Bergstrasse, Germany)
DO - 10.1002/chem.71456
UR - https://doi.org/10.1002/chem.71456
AB - 19F NMR is becoming an increasingly powerful method for studying the conformation and ligand binding of proteins in the solid state and in solution. In liquids NMR, surprisingly, reports on through‐space 19F–19F coupling remain scarce. Here, we present the first 19F–19F NOESY study designed to calibrate inter‐fluorine distances in proteins. Three difluorinated tryptophan analogues (4,5‐F2‐Trp, 4,6‐F2‐Trp, 5,6‐F2‐Trp) were synthesized and site‐specifically incorporated into human cyclophilin A (CypA). Series of 19F–19F NOESY build‐up experiments were recorded for each labeled protein, and the extracted cross‐relaxation rates were compared to fixed reference distances. While small distances in the 2.5–3.0 Å range were easily accessible, the upper limit at 14.1 T is ∼5 Å. These results provide evidence that short distances can be extracted from 19F–19F NOESY spectra, expanding the toolbox for studying protein‐protein or protein‐ligand interactions by NMR.
SN - 0947-6539
SN - 1521-3765
ER -