title: Labeled Ligand Displacement: Extending NMR-Based Screening of Protein Targets.
abstract: NMR spectroscopy has enjoyed widespread success as a method for screening protein targets, especially in the area of fragment-based drug discovery. However, current methods for NMR-based screening all suffer certain limitations. Two-dimensional methods like "SAR by NMR" require isotopically labeled protein and are limited to proteins less than about 50 kDa. For one-dimensional, ligand-based methods, results can be confounded by nonspecific compound binding, resonance overlap, or the need for a special NMR probe. We present here a ligand-based method that relies on the exchange broadening observed for a (13)C-labeled molecule upon binding to a protein target (labeled ligand displacement). This method can be used to screen both individual compounds and mixtures and is free of the artifacts inherent in other ligand-based methods.
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Swann
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064.
authors.forename: Danying
authors.initials: D
authors.lastname: Song
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064.
authors.forename: Chaohong
authors.initials: C
authors.lastname: Sun
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Hajduk
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Petros
keywords: NMR; fragment; labeling; ligand; screening