De Novo Designed Bifunctional Proteins for Targeted Protein Degradation
December 2025
TLDR Newly designed proteins can effectively degrade specific proteins in cells, offering a potential new therapy method.
This study explores the development of de novo designed bifunctional proteins as an alternative strategy for targeted protein degradation (TPD), aiming to overcome the limitations of current methods like PROTACs. The researchers created a stable helix-turn-helix scaffold capable of presenting various binding sites, using computational protein design to target BCL-xL and recruit the KLHL20 ligase. The designed proteins successfully bind to targets in vitro, and the bifunctional proteins effectively degrade BCL-xL in cells, inducing apoptosis. This approach potentially expands the range of targets and ligases accessible for therapeutic interventions.
