Cell-surface fucosylated glycan

Cell-surface fucosylated glycans are a diverse class of carbohydrate structures characterized by the covalent attachment of fucose residues to the termini or cores of glycoproteins and glycolipids on the plasma membrane. These glycans, which include the Lewis blood group antigens (e.g., Sialyl Lewis X and Sialyl Lewis A), play critical roles in physiological processes such as cell-cell adhesion, leukocyte trafficking, and signal transduction (Becker and Lowe, 2003). In many pathological conditions, particularly oncology, these glycans are aberrantly overexpressed, a hallmark that facilitates tumor metastasis by promoting adhesion to the vascular endothelium and aiding in immune evasion (J Transl Med, 2023). They also serve as receptors for various pathogens, including bacteria and viruses, which exploit these structures for host cell attachment and entry (Front. Mol. Biosci., 2024). Therapeutic strategies targeting these glycans include the use of selectin antagonists like uproleselan to block glycan-mediated adhesion, metabolic inhibitors such as 2-fluorofucose to deplete cellular fucose pools, and monoclonal antibodies designed to selectively target tumor-associated fucosylated epitopes (ACS, 2025). Additionally, specific fucosylated structures like AFP-L3 and CA19-9 are widely utilized as clinical biomarkers for cancer diagnosis and monitoring (NIH, 2017).

Other names

Fucosylated glycoconjugatesFucosylated oligosaccharidesLewis antigensFucosylated cell-surface carbohydratesFucosylated epitopes

Drugs targeting cell-surface fucosylated glycans primarily act through competitive antagonism of glycan-binding receptors (e.g., uproleselan blocking E-selectin), metabolic inhibition of fucose biosynthesis pathways to reduce glycan expression (e.g., 2-fluorofucose inhibiting GDP-fucose formation), and direct antibody-mediated targeting of tumor-associated fucosylated antigens to induce cell death via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC).