Associate Professor, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong (CUHK)
Chemically Induced Proximity for Targeted Protein O-GlcNAcylation
Host: S. Shi Boon
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.
International Seminar Programme
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