Rillahan, C.D., et al. Nat. Chem. Biol. 8, 661–668 (2012).

The transfer of a fucose or sialic acid sugar to a growing polysaccharide represents one step in a complex process that is poorly understood. Twenty sialyltransferases and 14 fucosyltransferases encoding variable acceptor specificities, activities and expression patterns are encoded in the human genome. To date, fluorinated analogs that block the transition state of these enzymes have not been membrane permeable, prompting Rillahan et al. to modify them by peracetylation. These protected analogs are neutrally charged and can slip into the cell, where sialic acid and fucose salvage pathway enzymes revert them to their unprotected form. The resulting membrane-permeable, family-specific inhibitors also shut down new biosynthesis through metabolic feedback, making them promising tools for dissecting the roles of fucosylated and sialylated glycans in cell communication and immunity.