Potent metabolic sialylation inhibitors based on C-5 modified fluorinated sialic acids
Research output: Contribution to journal › Journal article › Research › peer-review
Torben Heise, Johan Pijnenborg, Christian Büll, Niek van Hilten, Esther Kers-Rebel, Natasja Balneger, Hidde Elferink, Gosse J Adema, Thomas J Boltje
Sialic acid sugars on mammalian cells regulate numerous biological processes, while aberrant expression of sialic acid is associated with diseases like cancer and pathogenic infection. Inhibition of the sialic acid biosynthesis may therefore hold considerable therapeutic potential. To effectively decrease sialic acid expression, we synthesized C-5 modified 3-fluoro sialic acid sialyltransferase inhibitors. We found that C-5 carbamates significantly enhanced and prolonged the inhibitory activity in multiple mouse and human cell lines. As underlying mechanism, we have identified that carba-mate-modified 3-fluoro sialic acid inhibitors are more efficiently metabolized to their active CMP-analogs, reaching higher effective inhibitor concentrations inside cells.
|Journal||Journal of Medicinal Chemistry|
|Publication status||E-pub ahead of print - 2019|