ArticleACS medicinal chemistry letters2025
Beyond Isotopic Labeling: Expanding the Reach of Protein-Detect NMR in Lead Discovery.
Article in ACS medicinal chemistry letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Biophysical confirmation of the binding of small molecules to protein targets plays a critical role in lead discovery campaigns. While protein-detect NMR can provide binding confirmation over a range of affinities, it is especially useful, as opposed to other biophysical methods, for ligands which bind weakly to their protein targets, as is often the case early in the lead discovery process. However, the NMR approach, in its most robust form, requires the isotopic labeling of the protein, thus limiting its overall utility. Here we describe an approach to both confirm small-molecule binding and measure ligand affinities that does not require isotopic labeling of protein targets. This novel method utilizes 1D-diffusion filtered NMR followed by ECHOS analysis and will enable the use of protein-detect NMR to characterize ligand-protein interactions for many protein targets which are currently out of reach.
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