α2,6-linked sialic acid (α2,6-Sia)

α2,6-linked sialic acid residues are terminal monosaccharides found on cell-surface glycoproteins and glycolipids, primarily in the human upper respiratory tract (Varki et al., 2017). These residues are formed by the attachment of N-acetylneuraminic acid to a galactose residue via an α2,6-linkage, a process catalyzed by sialyltransferases such as ST6Gal-I. Biologically, they play a pivotal role in cell-cell recognition, immune system modulation, and the stabilization of protein conformations. They are most recognized as the primary attachment receptors for human-adapted influenza A and B viruses, which utilize their hemagglutinin protein to bind specifically to these linkages to initiate infection (Matrosovich et al., 2004). In oncology, over-expression of α2,6-sialylated glycans is frequently observed in various carcinomas and is associated with increased tumor invasiveness and poor prognosis (Bull et al., 2014). Therapeutic interventions include the use of host-directed sialidases like DAS181, which cleave these residues to block viral entry, and neuraminidase inhibitors that prevent the release of progeny virions from these sialic acid anchors (Moss et al., 2012).

Other names

Neu5Acα2-6GalAlpha-2,6-sialic acid6'-Sialyllactose epitopeSialic acid alpha-2,6-galactoseCD75

Enzymatic cleavage of sialic acid residues from the host cell surface to prevent viral binding, or inhibition of viral neuraminidase to prevent the cleavage of these residues, thereby trapping new virions on the cell surface.