First small-molecule PROTACs for G protein-coupled receptors: inducing α _1A-adrenergic receptor degradation.

ABSTRACT: Proteolysis targeting chimeras (PROTACs) are dual-functional hybrid molecules that can selectively recruit an E3 ubiquitin ligase to a target protein to direct the protein into the ubiquitin-proteasome system (UPS), thereby selectively reducing the target protein level by the ubiquitin-proteasome pathway. Nowadays, small-molecule PROTACs are gaining popularity as tools to degrade pathogenic protein. Herein, we present the first small-molecule PROTACs that can induce the α _1A-adrenergic receptor (α _1A-AR) degradation, which is also the first small-molecule PROTACs for G protein-coupled receptors (GPCRs) to our knowledge. These degradation inducers were developed through conjugation of known α ₁-adrenergic receptors (α ₁

SUBMITTER: Li Z 

PROVIDER: S-EPMC7563999 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature