Terminal cell-surface sialic acid residues on glycoconjugates (Sia)

Terminal cell-surface sialic acids are nine-carbon monosaccharides that typically occupy the outermost positions on the glycan chains of glycoproteins and glycolipids (Varki, A., 2008, Nature). These residues are essential for various biological processes, including cell-cell recognition, stabilization of protein conformation, and the regulation of immune cell signaling through interactions with Sialic acid-binding immunoglobulin-type lectins (Siglecs) (Crocker, P. R., et al., 2007, Nature Reviews Immunology). In many pathological states, such as cancer, cells exhibit hypersialylation, which contributes to tumor progression, metastasis, and immune evasion by creating a "sialic acid shield" that inhibits immune activation (Pearce, O. M., & Läubli, H., 2016, Glycobiology). Furthermore, terminal sialic acids serve as critical entry receptors for a variety of human pathogens, including influenza viruses, which bind to these residues via hemagglutinin to initiate infection (Matrosovich, M., et al., 2006, Virology). Therapeutic strategies targeting these residues include the use of sialidases like DAS181 to enzymatically strip sialic acids from the respiratory epithelium to prevent viral entry, and the development of sialyltransferase inhibitors to reduce hypersialylation in cancer (Gray, M. A., et al., 2020, Nature Chemical Biology). Neuraminidase inhibitors also play a role by preventing the cleavage of these residues, thereby trapping viral progeny on the host cell surface (Gubareva, L. V., 2004, The Lancet Infectious Diseases).

Other names

Sialic acidsN-acetylneuraminic acidNeu5AcSialyl groupsTerminal glycansSialic acid-containing glycans

The primary mechanisms of action involve the enzymatic removal of terminal sialic acids by sialidases (e.g., DAS181) to prevent pathogen binding, or the inhibition of viral neuraminidases (e.g., Oseltamivir) to prevent the cleavage of these residues, which traps viruses on the cell surface (Gubareva, L. V., 2004, The Lancet Infectious Diseases). In cancer, the focus is on inhibiting sialyltransferases to prevent hypersialylation or using sialidases to strip the "sialic acid shield" and enhance immune recognition (Gray, M. A., et al., 2020, Nature Chemical Biology).