Site-specific molecular glues for the 14-3-3/Tau pS214 protein-protein interaction <i>via</i> reversible covalent imine tethering.

ABSTRACT: Protein-protein interactions (PPIs) are key regulators of various cellular processes. Modulating PPIs with small molecules has gained increasing attention in drug discovery, particularly targeting the 14-3-3 protein family, which interacts with several hundred client proteins and plays a central role in cellular networks. However, targeting a specific PPI of the hub protein 14-3-3, with its plethora of potential client proteins, poses a significant selectivity challenge. This not only involves the selectivity of 14-3-3 PPIs with other client proteins, but also the selective stabilization of a specific 14-3-3 binding site within a protein partner featuring several binding sites. The interaction of 14-3-3 with Tau, characterized by different phospho-site driven binding modes, forms a valuabl

SUBMITTER: Oberheide A 

PROVIDER: S-EPMC11892739 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature