Brayley Gattis

Abstract Targeted protein degradation (TPD) has enabled modulation of previously undruggable proteins. However, existing small-molecule approaches require arduous optimization and are largely confined to targets bearing ligandable pockets. To address these challenges, we introduce the HYbrid DegRAding Copolymer (HYDRAC), a polymeric platform that integrates target‑binding peptides with peptide-based or small‑molecule degrons to orchestrate selective degradation of disease‑relevant proteins.

Abstract The burgeoning field of targeted protein degradation (TPD) has opened new avenues for modulating the activity of previously undruggable proteins of interest. To date, TPD has been dominated by small molecules containing separate linked domains for protein engagement and recruitment of cellular degradation machinery.