DNA-Programmable Protein Degradation: Dynamic Control of Proteolysis-Targeting Chimera Activity via DNA Hybridization and Strand Displacement.

ABSTRACT: Targeted protein degradation is a powerful therapeutic approach: expanding the druggable proteome, providing enhanced selectivity, and having the ability to overcome conventional resistance mechanisms. A major class of such molecules is proteolysis-targeting chimeras (PROTACs). PROTACs are catalytic heterobifunctional small molecules that simultaneously bind a protein of interest (POI) and an E3 ligase. And thus, PROTACs induce a proximity-dependent ubiquitination of the POI and its subsequent degradation by the ubiquitin-proteasome system. While PROTACs have successfully transitioned from academia to industry, increasing awareness of off-target effects and related toxicities highlights the urgent need for precise control mechanisms over activity. Achieving this level of control, however,

SUBMITTER: Kashyap D 

PROVIDER: S-EPMC12381747 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature