Detection of Protein-Ligand Interactions by ¹⁹F Nuclear Magnetic Resonance Using Hyperpolarized Water

The transfer of nuclear spin hyperpolarization from water to ligand ¹⁹F spins results in a transient signal change that is indicative of protein-ligand interaction. The ¹⁹F nucleus allows for background-free detection of these signals, which are modulated by polarization transfer via pathways similar to those in a hyperpolarized ¹H water LOGSY experiment. Quantification of the apparent heteronuclear cross-relaxation rates is facilitated by a simultaneous dual-channel detection of ¹H and ¹⁹F signals. Calculated cross-relaxation rates for the ¹H-¹⁹F transfer step indicate that these rates are sensitive to binding to medium- and large-sized proteins. The heteronuclear observation of hyperpolarization transfer from water may be used to screen protein-ligand interactions in drug discovery and other applications.