Sialic acid residues on sialoglycans (Sia)

Sialic acid residues are nine-carbon acidic monosaccharides typically located at the terminal positions of glycan chains on cell-surface glycoproteins and glycolipids (Varki, 2008). They play a critical role in biological recognition, serving as ligands for various receptors, including the Siglec (Sialic acid-binding immunoglobulin-type lectin) family, which regulates immune cell activity and maintains self-tolerance (Pearce & Läubli, 2016). In the context of infectious diseases, sialic acids serve as essential attachment points for pathogens like the influenza virus, which utilizes hemagglutinin to bind and neuraminidase to cleave these residues during viral egress (Varki, 2008). In oncology, many tumors exhibit hypersialylation, a process where an overabundance of sialic acids creates an "immunosuppressive shield" that inhibits immune cell activation (such as T cells and NK cells) through the engagement of inhibitory Siglecs (Palleon Pharmaceuticals, 2023). Therapeutic strategies targeting these residues include neuraminidase inhibitors for viral infections and sialidase-based "glyco-immune checkpoint" inhibitors, such as E-602, designed to desialylate the tumor microenvironment and enhance anti-tumor immunity (Gray et al., 2020).

Other names

N-acetylneuraminic acidNeu5AcSialic acidsSialoglycansSialylated glycansTerminal sialic acids

Therapeutic strategies involve the enzymatic cleavage of terminal sialic acid residues (desialylation) to remove immunosuppressive signals or the inhibition of viral neuraminidases to prevent the cleavage of these residues, thereby trapping viral particles on the host cell surface. Some agents also aim to block the binding of sialic acids to inhibitory Siglec receptors on immune cells.