Cell-surface sialic acid-containing receptors

Cell-surface sialic acid-containing receptors are a heterogeneous class of glycoconjugates, including glycoproteins and glycolipids, that display terminal sialic acid residues on their extracellular glycan chains (Varki, 2008). These molecules are ubiquitous on vertebrate cell surfaces and serve as critical mediators of biological recognition and signaling (Varki, 2008). In the context of infectious diseases, they act as the primary attachment points for various pathogens, including influenza viruses and certain coronaviruses, which utilize their surface proteins to bind specific sialic acid linkages (Gamblin & Skehel, 2010). In oncology, the over-expression of these sialic acids, known as hypersialylation, on tumor cells contributes to immune evasion by interacting with inhibitory Siglec receptors on immune cells (Läubli & Varki, 2020). This interaction creates an immunosuppressive microenvironment that protects the tumor from the host's immune system (Läubli & Varki, 2020). Therapeutic strategies targeting these receptors include the use of sialidases, such as DAS181, which enzymatically remove the sialic acid residues to prevent viral entry (Malakhov et al., 2006). Additionally, novel glyco-immune checkpoint inhibitors like E-602 are being developed to desialylate the tumor microenvironment and restore anti-tumor immunity (Palleon Pharmaceuticals, 2024). These approaches represent a shift toward targeting the host-pathogen or host-tumor interface by modifying the cell surface glycome.

Other names

Sialylated glycoconjugatesSialosidesSialic acid-bearing receptorsSialic acid ligandsHost cell sialic acids

Enzymatic removal of terminal sialic acid residues from host cell surface glycoconjugates to prevent pathogen attachment or to modulate immune signaling.