Molecular features defining the efficiency of bioPROTACs.

ABSTRACT: BioPROTACs consist of a target-binding unit and a component of the ubiquitin-proteasome system. However, the specific biophysical features influencing their effectiveness are poorly understood. We investigated the design principles defining the target-binding moiety of bioPROTACs. We used our recently developed assay for accurately measuring degradation rates, based on microinjection and live-cell microscopy, independent of other confounding factors like biosynthesis and transport. We used a very efficient UPS interaction domain from CHIP E3 ligase, and 9 different well-characterized DARPins to test degradation of the proof-of-principle target eGFP. All but two DARPins work well in this context, one sterically preventing E2 binding in the complex, the other overlapping with the target ubiq

SUBMITTER: Winkelvoß D 

PROVIDER: S-EPMC12181330 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature