Terminal α2,3- or α2,6-linked sialic acid on cell-surface sialoglycan

Terminal α2,3- and α2,6-linked sialic acids are negatively charged monosaccharides positioned at the outermost ends of glycoproteins and glycolipids on mammalian cell surfaces[6][7]. Their linkage and density influence the physical and biological properties of cells, such as anti-adhesion (resisting unwanted cell aggregation), molecular recognition, and immune modulation[1][3]. These sialoglycans are critical for normal development, regulation of immune cell signaling (particularly through Siglec family receptors), and host protection from complement activation[2][9]. In cancer, high-density sialoglycans contribute to immune evasion and metastasis[6][7]. Many pathogens, including influenza viruses and coronaviruses, exploit terminal sialic acids for cell entry[8]. Their unique specificity (α2,3 versus α2,6 linkages) determines which cell types are targeted, influencing host-pathogen specificity and immune responses[4][6][5]. These motifs are thus a validated target in cancer, infectious disease, and immunological research, with several drugs in use or development that modulate sialic acid recognition or biosynthesis pathways. However, due to their ubiquitous presence and essential physiological functions, targeting must be precise to avoid broad immune or developmental disruption[6][9].

Other names

Terminal sialic acidSialoglycan (terminal)α2,3-linked sialic acidα2,6-linked sialic acidNeu5Ac (N-acetylneuraminic acid) terminal glycans

Inhibition of pathogen binding and cell entry by blocking sialic acid-mediated attachment Modulation of immune responses via Siglec agonism/antagonism Altering cell adhesion and migration by modifying sialylation state