Assessment of Attainable Distances in Proteins by Through-Space ¹⁹F-¹⁹F Couplings.

Authors

Iker Hernández, In-Ja L Byeon, Christina M Monnie, Vadim A Soloshonok, Aitor Landa, Mikel Oiarbide, Angela M Gronenborn

Published in

Chemistry (Weinheim an der Bergstrasse, Germany). Pages e71456. Jul 24, 2026. Epub Jul 24, 2026.

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.

PMID:
42497074
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.

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