Chemistry

Cell

Enzyme

Sialyltransferase

Cell culture

Sialic acid

Biology

Genetics

Biosynthesis

Cytidine

Biochemistry

Journal of Medicinal Chemistry

Sialic acid sugars on mammalian cells regulate numerous biological processes, while aberrant expression of sialic acid is associated with diseases such as cancer and pathogenic infection. Inhibition of the sialic acid biosynthesis may therefore hold considerable therapeutic potential. To effectively decrease the 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 an underlying mechanism, we have identified that carbamate-modified 3-fluoro sialic acid inhibitors are more efficiently metabolized to their active cytidine monophosphate analogues, reaching higher effective inhibitor concentrations inside cells.

Potent Metabolic Sialylation Inhibitors Based on C-5-Modified Fluorinated Sialic Acids