Intracellular Hydrolysis of Small-Molecule -Linked -Acetylglucosamine Transferase Inhibitors Differs among Cells and Is Not Required for Its Inhibition.

-GlcNAcylation is an essential post-translational modification that occurs on nuclear and cytoplasmic proteins, regulating their function in response to cellular stress and altered nutrient availability. -GlcNAc transferase (OGT) is the enzyme that catalyzes this reaction and represents a potential therapeutic target, whose biological role is still not fully understood. To support this research field, a series of cell-permeable, low-nanomolar OGT inhibitors were recently reported.