α2,6-linked sialic acid-containing glycans (α2,6-Sia)

α2,6-linked sialic acid-containing glycans are complex carbohydrates found at the terminal ends of glycoproteins and glycolipids on the surface of mammalian cells (Varki et al., 2015, Essentials of Glycobiology). In these structures, N-acetylneuraminic acid is attached to the penultimate galactose residue via an α2,6-glycosidic bond, a linkage catalyzed by the enzyme beta-galactoside alpha-2,6-sialyltransferase 1 (ST6Gal-I) (Harduin-Lepers et al., 2001, Glycobiology). These glycans serve as the primary attachment receptors for human-adapted influenza viruses, which utilize their hemagglutinin protein to bind specifically to α2,6-linkages rather than the α2,3-linkages preferred by avian strains (Shinya et al., 2006, Nature). Beyond viral entry, these glycans play significant roles in modulating immune cell signaling, particularly through interactions with Siglecs (sialic acid-binding immunoglobulin-type lectins) which regulate the threshold of immune cell activation (Crocker et al., 2007, Nature Reviews Immunology). In oncology, the upregulation of α2,6-sialylation is often associated with increased tumor invasiveness, metastasis, and resistance to apoptosis (Pietrobono et al., 2020, International Journal of Molecular Sciences). Therapeutic strategies targeting these glycans include the use of recombinant sialidases like DAS181 to remove the sugar residues from the respiratory epithelium or the development of neuraminidase inhibitors that prevent viruses from detaching from these receptors (Moss et al., 2012, Journal of Infectious Diseases).

Other names

Alpha-2,6-sialic acidNeu5Acα2-6Gal6'-Sialyllactose-containing glycansSialic acid alpha 2-6 galactoseα2,6-linked N-acetylneuraminic acid

Enzymatic removal of terminal sialic acids from the host cell surface to prevent viral attachment; inhibition of viral neuraminidase to prevent the release of progeny virions from sialic acid receptors; competitive binding to block viral hemagglutinin interaction.