Targeted Protein O-GlcNAcylation Using Bifunctional Small Molecules.

ABSTRACT: Protein O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) plays a crucial role in regulating essential cellular processes. The disruption of the homeostasis of O-GlcNAcylation has been linked to various human diseases, including cancer, diabetes, and neurodegeneration. However, there are limited chemical tools for protein- and site-specific O-GlcNAc modification, rendering the precise study of the O-GlcNAcylation challenging. To address this, we have developed heterobifunctional small molecules, named O-GlcNAcylation TArgeting Chimeras (OGTACs), which enable protein-specific O-GlcNAcylation in living cells. OGTACs promote O-GlcNAcylation of proteins such as BRD4, CK2α, and EZH2 in cellulo by recruiting FKBP12^F36V-fused O-GlcNAc transferase (OGT), with t

SUBMITTER: Ma B 

PROVIDER: S-EPMC11009946 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature