Chemical tools to track and perturb the expression of sialic acid and fucose monosaccharides

Abstract

The biosynthesis of glycans is a highly conserved biological process and found in all domains of life. The expression of cell surface glycans is increasingly recognized as a target for therapeutic intervention given the role of glycans in major pathologies such as cancer and microbial infection. Herein, we summarize our contributions to the development of unnatural monosaccharide derivatives to infiltrate and alter the expression of both mammalian and bacterial glycans and their therapeutic application.

Fig. 1. Overview of the therapeutic strategies targeting glycosylation.

Fig. 2. Overview of the fucose biosynthesis and inhibitors targeting the salvage and de novo biosynthesis pathway.

Fig. 3. Overview of sialic acid biosynthesis and inhibitors targeting the salvage and de novo pathways.

Fig. 4. Metabolic labeling of cell surface sialic acid residues to introduce high affinity Siglec ligands using bioorthogonal chemistry.

Fig. 5. Metabolic labelling of sialic acids to track and perturb viral infections utilizing sialic acid expression.

Fig. 6. Metabolic labels and inhibitors based on bacterial monosaccharides.

Fig. 7. Metabolic labels and inhibitors to track and inhibit the sialic acid utilization in bacteria.