Ligand-Directed Self-Assembling Chimeras for Targeted Protein O-GlcNAcylation.

ABSTRACT: Precise control of protein-specific O-GlcNAcylation in cells remains a major challenge. Chemically induced proximity (CIP) offers a promising path forward, but its application to targeted protein O-GlcNAcylation has been limited by the lack of ligands that can bind the O-GlcNAc transferase (OGT) without inhibiting its catalytic function. Here, we repurpose a potent OGT inhibitor into a noninhibitory covalent probe using ligand-directed release chemistry (LDR). The resulting ligands covalently label OGT while preserving its enzymatic activity. Building on this scaffold, we developed a self-assembling O-GlcNAcylation Targeting Chimera (OGTAC) that recruits OGT to its native substrate casein kinase IIα (CK2α) in living cells, selectively elevating CK2α O-GlcNAcylation without affecting global

SUBMITTER: Guo Z 

PROVIDER: S-EPMC12723682 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature