Fluorescence Anisotropy-Based Tethering for Discovery of Protein-Protein Interaction Stabilizers.

ABSTRACT: Protein-protein interaction (PPI) networks are fundamental for cellular processes. Small-molecule PPI enhancers have been shown to be powerful tools to fundamentally study PPIs and as starting points for potential new therapeutics. Yet, systematic approaches for their discovery are not widely available, and the design prerequisites of "molecular glues" are poorly understood. Covalent fragment-based screening can identify chemical starting points for these enhancers at specific sites in PPI interfaces. We recently reported a mass spectrometry-based disulfide-trapping (tethering) approach for a cysteine residue in the hub protein 14-3-3, an important regulator of phosphorylated client proteins. Here, we invert the strategy and report the development of a functional read-out for systematic id

SUBMITTER: Sijbesma E 

PROVIDER: S-EPMC7754187 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature