Peptide-Based PROTACs: Transitioning from Static Paradigm to a Dynamic Landscape in Targeted Protein Degradation

The document reviews the advancements and potential of peptide-based PROTACs (pPROTACs) in targeted protein degradation, emphasizing their ability to target "undruggable" proteins and offering advantages over small-molecule PROTACs. Recent innovations, such as improved cell permeability, stability, and modular design, enhance their therapeutic potential, particularly in cancer therapy and other medical applications. Strategies like self-assembling pPROTACs and bioPROTACs expand their design space, while integration with technologies like AI-driven design and nanotechnology promises further enhancements. Despite challenges in delivery and stability, pPROTACs are poised to become versatile platforms in precision medicine, with ongoing research supported by multiple institutions and grants.