Hyperpolarized Water to Study Protein-Ligand Interactions

J Phys Chem Lett. 2015 May 7;6(9):1674-8. doi: 10.1021/acs.jpclett.5b00403. Epub 2015 Apr 20.

Abstract

The affinity between a chosen target protein and small molecules is a key aspect of drug discovery. Screening by popular NMR methods such as Water-LOGSY suffers from low sensitivity and from false positives caused by aggregated or denatured proteins. This work demonstrates that the sensitivity of Water-LOGSY can be greatly boosted by injecting hyperpolarized water into solutions of proteins and ligands. Ligand binding can be detected in a few seconds, whereas about 30 min is usually required without hyperpolarization. Hyperpolarized water also enhances proton signals of proteins at concentrations below 20 μM so that one can verify in a few seconds whether the proteins remain intact or have been denatured.

Keywords: Water-LOGSY; drug discovery; dynamic nuclear polarization; hyperpolarization; nuclear magnetic resonance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ligands
  • Protein Binding
  • Proteins / chemistry*

Substances

  • Ligands
  • Proteins