Special Seminar: “Targeted Protein O-GlcNAcylation: A Chemist’s Perspective”
Talk Title: “Targeted Protein O-GlcNAcylation: A Chemist’s Perspective”
Speaker:
Billy Wai-Lung Ng, PhD (View CV)
Assistant Professor
School of Pharmacy, Faculty of Medicine
The Chinese University of Hong Kong
Location: Room W302, New Research Building
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 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 FKBP12F36V-fused 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.
Lecture Contacts:
Junfeng Ma (Junfeng.Ma@georgetown.edu) and Huadong Pei (huadong.pei@georgetown.edu)