Molecularly Built Ligands Degrade Membrane Receptors via Enhancing Their Accumulation in Lysosomes.

ABSTRACT: This study presents molecularly built ligand-based lysosome-targeting chimeras (MBL-LYTACs) as a versatile platform for membrane receptor degradation. MBL-LYTACs are engineered by conjugating targeting ligands (e.g., small molecules, oligopeptides, aptamers, nanobodies, and antibodies) with lysosome-localized molecules. Functional screening and mechanistic studies reveal that MBL-LYTACs significantly enhance internalization and lysosomal accumulation of membrane receptors, including folate receptor α, programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), and protein tyrosine kinase 7 (PTK7), by leveraging morpholine, dimethylethanamine, or low-polymerized mPEGs as lysosome-localized moieties, leading to receptor degradation. This approach eliminates reliance on cell-s

SUBMITTER: Zhang D 

PROVIDER: S-EPMC12746154 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature