Heterobifunctional proteomimetic polymers for targeted degradation of MYC and KRAS.

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. HYDRACs are amenable to scalable synthetic methods, exhibit broad structural tunability, and support multivalent payload conjugation. This intrinsic modularity enables incorporation of a diverse repertoire of target‑binding motifs and E3‑ligase recruiters. These include von Hippel-Lindau protein (VHL), Kelch-lik

SUBMITTER: Wang MM 

PROVIDER: S-EPMC12932639 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature