Browsing by Author "Ma, Dawei"
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Item Open Access A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress.(Science (New York, N.Y.), 2005-02) Boyce, Michael; Bryant, Kevin F; Jousse, Céline; Long, Kai; Harding, Heather P; Scheuner, Donalyn; Kaufman, Randal J; Ma, Dawei; Coen, Donald M; Ron, David; Yuan, JunyingMost protein phosphatases have little intrinsic substrate specificity, making selective pharmacological inhibition of specific dephosphorylation reactions a challenging problem. In a screen for small molecules that protect cells from endoplasmic reticulum (ER) stress, we identified salubrinal, a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit alpha (eIF2alpha). Salubrinal also blocks eIF2alpha dephosphorylation mediated by a herpes simplex virus protein and inhibits viral replication. These results suggest that selective chemical inhibitors of eIF2alpha dephosphorylation may be useful in diseases involving ER stress or viral infection. More broadly, salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events.Item Open Access Structure-activity relationship studies of salubrinal lead to its active biotinylated derivative.(Bioorganic & medicinal chemistry letters, 2005-09) Long, Kai; Boyce, Michael; Lin, He; Yuan, Junying; Ma, DaweiThe synthesis and structure-activity relationships (SAR) of salubrinal, a small molecule that protects cells from apoptosis induced by endoplasmic reticulum (ER) stress, are described. It is revealed that the trichloromethyl group greatly contributes to the activity. Based on the SAR results, salubrinal was converted into a biotinylated derivative which retains activity and can be used as a biological tool for target identification.