Work

Detection of an Antagonist Bound to the Neurokinin a Receptor in Styrene–Maleic Acid Lipid Particles by 19 F Ultrafast Magic‐Angle Spinning Nuclear Magnetic Resonance Spectroscopy

Year: 2026

Type: article

Abstract: G protein‐coupled receptors (GPCRs) are major pharmacological targets, with ≈34% of FDA‐approved drugs acting on this protein family. The frequent incorporation of fluorine into small‐molecule ligands enables the use of 19 F nuclear magnetic resonance (NMR) as a sensitive and site‐specific method to probe ligand behaviour. In this case study, we investigate the fluorinated antagonist GR159897 bound to the membrane‐embedded neurokinin A receptor reconstituted in detergent‐free styrene–maleic acid lipid particles (SMALPs) using 19 F ultrafast magic‐angle spinning (MAS) solid‐state NMR. We demonstrate that the environmental sensitivity of 19 F NMR resolves distinct ligand populations within the SMALP system and enables detection of receptor‐associated ligand, highlighting the utility of 19 F solid‐state NMR for probing GPCR–ligand interactions.

Source: ChemBioChem

DOI: 10.1002/cbic.202500963