Combined Protein- and Ligand-Observed NMR Workflow to Screen Fragment Cocktails against Multiple Proteins: A Case Study Using Bromodomains.

ABSTRACT: As fragment-based drug discovery has become mainstream, there has been an increase in various screening methodologies. Protein-observed ¹⁹F (PrOF) NMR and ¹H CPMG NMR are two fragment screening assays that have complementary advantages. Here, we sought to combine these two NMR-based assays into a new screening workflow. This combination of protein- and ligand-observed experiments allows for a time- and resource-efficient multiplexed screen of mixtures of fragments and proteins. PrOF NMR is first used to screen mixtures against two proteins. Hit mixtures for each protein are identified then deconvoluted using ¹H CPMG NMR. We demonstrate the benefit of this fragment screening method by conducting the first reported fragment screens against the bromodomains of

SUBMITTER: Johnson JA 

PROVIDER: S-EPMC7504435 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature