Cell-surface α2,3- and α2,6-linked sialic acid residues (α2,3/α2,6-Sia)

Cell-surface α2,3- and α2,6-linked sialic acid residues are terminal monosaccharides found on the glycan chains of glycoproteins and glycolipids. These residues play a critical role in biological recognition, serving as essential receptors for various pathogens, most notably the influenza virus, where α2,3-linkages are preferred by avian strains and α2,6-linkages by human strains (Long et al., 2019). In the context of oncology, many tumors exhibit hypersialylation, a process where an overabundance of these residues creates a "glycan shield" that interacts with Siglec receptors on immune cells to suppress the anti-tumor immune response (Läubli & Varki, 2020). Therapeutic strategies targeting these residues include the use of neuraminidase inhibitors to block viral egress and engineered sialidases, such as E-602, to strip these residues from the surface of cancer cells, thereby enhancing immune detection (Palleon Pharmaceuticals, 2023). Additionally, these residues are involved in cell-cell adhesion and inflammatory signaling pathways (Varki, 2008). Understanding the distribution and linkage types of these sialic acids is vital for developing targeted anti-infectives and next-generation cancer immunotherapies.

Other names

Sialic acid residuesNeu5Ac glycansSialylated glycoproteinsInfluenza virus receptorsSiglec ligandsα2,3-Siaα2,6-Sia

Enzymatic removal of sialic acid residues (desialylation) to prevent pathogen entry or disrupt immune-suppressive Siglec signaling; competitive inhibition of viral neuraminidase to prevent the release of viral progeny from sialylated host cell surfaces.