Heterobifunctional small degrader molecules that tether endogenous E3 ubiquitin ligases are promising substrates for targeted protein degradation, however, the precise formation of the E3 ligase–target complex remains challenging and limits their application. Here, the authors introduce indirect ubiquitination of the target proteins via non-covalent interactions that bypass E3 ligases, enabling efficient protein degradation.
- Takafumi Furuhata
- Kazuki Yoshida
- Akimitsu Okamoto
