Chen Peng, Andrew T Namanja, Eva Munoz, Haihong Wu, Thomas E Frederick, Mitcheell Maestre-Martinez, Isaac Iglesias Fernandez, Qi Sun, Carlos Cobas, Chaohong Sun, Andrew M Petros
Fragment-based drug discovery (FBDD) and validation of small molecule binders using NMR spectroscopy is an established and widely used method in the early stages of drug discovery. Starting from a library of small compounds, ligand- or protein-observed NMR methods are employed to detect binders, typically weak, that become the starting points for structure-activity relationships (SAR) by NMR. Unlike the more frequently used ligand-observed 1D NMR techniques, protein-observed 2D 1 H-15 N or 1 H-13 C heteronuclear correlation (HSQC or HMQC) methods offer insights that include the mechanism of ligand engagement on the target and direct binding affinity measurements in addition to routine screening...
December 13, 2022: Journal of Biomolecular NMR