Sialosides on cell-surface glycoproteins (Sialosides)

Sialosides on cell-surface glycoproteins are terminal sugar residues, predominantly N-acetylneuraminic acid (Neu5Ac), that decorate the glycan chains of membrane-bound proteins and lipids (Varki et al., Essentials of Glycobiology, 2017). These molecules function as critical components of the biological glyco-code, mediating cell-cell recognition and signaling by serving as ligands for receptors such as Siglecs (Sialic acid-binding immunoglobulin-type lectins) and selectins (Duenas et al., 2020). In many malignancies, an overabundance of these sialosides, known as hypersialylation, acts as a glyco-immune checkpoint that suppresses the immune response by engaging inhibitory Siglecs on natural killer (NK) cells and macrophages (Palleon Pharmaceuticals, 2024; Iwasaki et al., 2021). Beyond oncology, sialosides are essential for the attachment and entry of various pathogens, most notably the influenza virus, which utilizes hemagglutinin to bind specific sialic acid linkages (PubMed, 2021). Therapeutic interventions include sialidase fusion proteins, such as E-602, which enzymatically strip sialosides to restore anti-tumor immunity, and neuraminidase inhibitors like Oseltamivir that block viral propagation (Palleon Pharmaceuticals, 2024; NIH, 2023). However, targeting these molecules presents challenges, such as the risk of thrombocytopenia caused by the accelerated clearance of desialylated platelets in the liver (Sorensen et al., 2009).

Other names

SialoglycansSialic acid-containing glycansCell-surface sialoglycoproteinsN-acetylneuraminic acid conjugatesSialylated glycans

Therapeutic strategies primarily involve enzymatic desialylation to remove terminal sialic acids from the cell surface or inhibiting viral neuraminidases to prevent the cleavage of sialosides, thereby modulating immune signaling or blocking viral release.