Reversible Covalent Imine-Tethering for Selective Stabilization of 14-3-3 Hub Protein Interactions.

ABSTRACT: The stabilization of protein complexes has emerged as a promising modality, expanding the number of entry points for novel therapeutic intervention. Targeting proteins that mediate protein-protein interactions (PPIs), such as hub proteins, is equally challenging and rewarding as they offer an intervention platform for a variety of diseases, due to their large interactome. 14-3-3 hub proteins bind phosphorylated motifs of their interaction partners in a conserved binding channel. The 14-3-3 PPI interface is consequently only diversified by its different interaction partners. Therefore, it is essential to consider, additionally to the potency, also the selectivity of stabilizer molecules. Targeting a lysine residue at the interface of the composite 14-3-3 complex, which can be targeted expli

SUBMITTER: Cossar PJ 

PROVIDER: S-EPMC8193639 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature