Modulation of Protein-Protein Interactions with Molecular Glues in a Synthetic Condensate Platform.

ABSTRACT: Misregulation of protein-protein interactions (PPIs) underlies many diseases; hence, molecules that stabilize PPIs, known as molecular glues, are promising drug candidates. Identification of novel molecular glues is highly challenging among others because classical biochemical assays in dilute aqueous conditions have limitations for evaluating weak PPIs and their stabilization by molecular glues. This hampers the systematic discovery and evaluation of molecular glues. Here, we present a synthetic condensate platform for the study of PPIs and molecular glues in a crowded macromolecular environment that more closely resembles the dense cellular milieu. With this platform, weak PPIs can be enhanced by sequestration. The condensates, based on amylose derivatives, recruit the hub protein 14-3-3

SUBMITTER: van Veldhuisen TW 

PROVIDER: S-EPMC11826995 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature