Matthew Pratt

“Chemical Probes for the Functional Analysis of O-GlcNAc Modifications in Human Disease”

The modification of proteins in the cytosol, nucleus, and mitochondria by the monosaccharide N-acetyl-glucosamine (O-GlcNAc) is required for development in mammals and Drosophila and is misregulated in a variety of diseases, including cancer and neurodegeneration. One of the general functions of O-GlcNAcylation is to respond to changes in metabolism and cellular stress. Here I will present the use of both chemical reporters and synthetic protein chemistry to investigate how O-GlcNAcylation levels become increased during oxidative stress, how this increase promotes cell-survival in cancer, and how O-GlcNAcylation blocks the aggregation of the Parkinson’s disease associated protein α-synuclein.