Drug Screening in Human Cells by NMR Spectroscopy Allows the Early Assessment of Drug Potency.

ABSTRACT: Structure-based drug development is often hampered by the lack of in vivo activity of promising compounds screened in vitro, due to low membrane permeability or poor intracellular binding selectivity. Herein, we show that ligand screening can be performed in living human cells by "intracellular protein-observed" NMR spectroscopy, without requiring enzymatic activity measurements or other cellular assays. Quantitative binding information is obtained by fast, inexpensive ¹ H NMR experiments, providing intracellular dose- and time-dependent ligand binding curves, from which kinetic and thermodynamic parameters linked to cell permeability and binding affinity and selectivity are obtained. The approach was applied to carbonic anhydrase and, in principle, can be extended to any NMR-ob

SUBMITTER: Luchinat E 

PROVIDER: S-EPMC7187179 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature