Int'l Centre for Genetic Eng. and Biotechnology 91d ago

Billy Ng, Associate Professor, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong (CUHK) speaks on "Chemically Induced Proximity for Targeted Protein O-GlcNAcylation". Abstract Protein O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) plays a crucial role in regulating essential cellular processes. The disruption of O-GlcNAcylation homeostasis 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 O-GlcNAcylation challenging. To address this, we have developed bifunctional 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 p53, BRD4, CK2α, and EZH2 in cellulo by recruiting O-GlcNAc transferase (OGT), with temporal, magnitude, and reversible control. Overall, OGTACs represent a promising approach for inducing protein-specific O-GlcNAcylation, thus enabling functional dissection and offering new directions for O-GlcNAc-targeting therapeutic development.