The sugar modification O-linked N-acetyl glucosamine (O-GlcNAc) is a nutrient sensor that cells and organisms use to maintain essential biological processes. Dysregulation of O-GlcNAc is linked to disruptions in essential biological processes, including sleep and circadian rhythm, and neurodegenerative diseases like Alzheimer’s disease and Parkinson's disease. In order to explore the role of O-GlcNAc on glycoproteins in human disease, we have now developed a cellular approach for writing and erasing O-GlcNAc from target proteins in the cell. The method uses a nanobody fused to an O-GlcNAc writer or eraser to control O-GlcNAc levels on the desired target protein. Here I will describe current efforts to measure, map, and manipulate O-GlcNAc from desired target proteins in a cell type specific manner to yield crucial insights to contribution of O-GlcNAc to disease, and novel chemical strategies for remediation.

Selective installation of O-GlcNAc on target proteins and cells

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ACS Spring 2023

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