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- W2179833949 abstract "Alpha-dystroglycan (α-DG), a highly glycosylated receptor for extracellular matrix proteins, plays a critical role in many biological processes. Hypoglycosylation of α-DG results in various types of muscular dystrophies and is also highly associated with progression of majority of cancers. Currently, there are no effective treatments for those devastating diseases. Enhancing functional O-mannosyl glycans (FOG) of α-DG on the cell surfaces is a potential approach to address this unmet challenge. Based on the hypothesis that the cells can up-regulate FOG of α-DG in response to certain chemical stimuli, we developed a cell-based high-throughput screening (HTS) platform for searching chemical enhancers of FOG of α-DG from a large chemical library with 364,168 compounds. Sequential validation of the hits from a primary screening campaign and chemical works led to identification of a cluster of compounds that positively modulate FOG of α-DG on various cell surfaces including patient-derived myoblasts. These compounds enhance FOG of α-DG by almost ten folds, which provide us powerful tools for O-mannosylation studies and potential starting points for the development of drug to treat dystroglycanopathy." @default.
- W2179833949 created "2016-06-24" @default.
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- W2179833949 date "2015-12-01" @default.
- W2179833949 modified "2023-10-16" @default.
- W2179833949 title "Small molecules enhance functional O-mannosylation of Alpha-dystroglycan" @default.
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- W2179833949 doi "https://doi.org/10.1016/j.bmc.2015.11.011" @default.
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