Hyperpolarized Water to Study Protein-Ligand Interactions.
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.
†Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Quentin
Q
Chappuis
†Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Jonas
J
Milani
†Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Basile
B
Vuichoud
†Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Aurélien
A
Bornet
‡Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland.
Alvar D
AD
Gossert
†Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.|§Département de Chimie, Ecole Normale Supérieure, PSL, 75005 Paris, France.|⊥Sorbonne Université, UPMC Univ Paris 06, 75005 Paris, France.|#Laboratoire des BioMolécules, UMR 7203, 75005 Paris, France.
Geoffrey
G
Bodenhausen
†Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.|∥Bruker BioSpin AG, 8117 Fällanden, Switzerland.
Sami
S
Jannin
D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*
D008024:Ligands; D011506:Proteins
Water-LOGSY; drug discovery; dynamic nuclear polarization; hyperpolarization; nuclear magnetic resonance