Single-Molecule-Based, Label-Free Monitoring of Molecular Glue Efficacies for Promoting Protein-Protein Interactions Using YaxAB Nanopores.

ABSTRACT: Modulating protein-protein interactions (PPIs) is an attractive strategy in drug discovery. Molecular glues, bifunctional small-molecule drugs that promote PPIs, offer an approach to targeting traditionally undruggable targets. However, the efficient discovery of molecular glues has been hampered by the current limitations of conventional ensemble-averaging-based methods. In this study, we present a YaxAB nanopore for probing the efficacy of molecular glues in inducing PPIs. Using YaxAB nanopores, we demonstrate single-molecule-based, label-free monitoring of protein complex formation between mammalian target of rapamycin (mTOR) and FK506-binding proteins (FKBPs) triggered by the molecular glue, rapamycin. Owing to its wide entrance and adjustable pore size, in combination with potent elec

SUBMITTER: Ryu M 

PROVIDER: S-EPMC11562796 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature