Detection of Protein–Ligand Interactions by <sup>19</sup>F Nuclear Magnetic Resonance Using Hyperpolarized Water
Jiandu Hu, Jihyun Kim, Christian Hilty
Abstract
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.