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

The transfer of nuclear spin hyperpolarization from water to ligand 19 F spins results in a transient signal change that is indicative of protein-ligand interaction. The 19 F nucleus allows for background-free detection of these signals, which are modulated by polarization transfer via pathways similar to those in a hyperpolarized 1 H water LOGSY experiment. Quantification of the apparent heteronuclear cross-relaxation rates is facilitated by a simultaneous dual-channel detection of 1 H and 19 F signals. Calculated cross-relaxation rates for the 1 H- 19 F 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.