Non-invasive in vivo monitoring of PROTAC-mediated protein degradation using an environment-sensitive reporter.

ABSTRACT: Proteolysis targeting chimeras (PROTACs) represent a groundbreaking therapeutic technology for selectively degrading proteins of interest (POIs). The structural variations in PROTACs unpredictably influence their protein degradation efficiency, which is predominantly assessed by quantifying POIs abundance through western blotting. This approach, however, falls short of enabling non-invasive monitoring of protein degradation within living cells let alone assessing directly the degradation effects in vivo. Herein, we develop an environment-sensitive reporter (ESR) for the quantification of protein degradation events triggered by PROTACs in vivo. By simultaneously integrating POIs targeting ligand and an environment-sensitive fluorophore, the ESR signals exhibit a strong fluorescence correlat

SUBMITTER: Li T 

PROVIDER: S-EPMC11846984 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature