Cell-surface glycans with terminal galactose

Cell-surface glycans with terminal galactose (frequently referred to as N-terminal galactose in the context of N-linked glycosylation) are carbohydrate structures located at the non-reducing ends of glycoproteins and glycolipids. These glycans serve as critical attachment factors and primary receptors for several biological entities, most notably the adeno-associated virus serotype 9 (AAV9), which utilizes terminal galactose for cell entry and tissue tropism. This interaction is the basis for AAV9-mediated gene therapies, such as onasemnogene abeparvovec, which target the central nervous system and heart. Additionally, terminal galactose residues are the primary ligands for galectins, a family of carbohydrate-binding proteins like Galectin-3 that regulate cell signaling, adhesion, and the formation of the galectin lattice. In pathological states, particularly cancer, the desialylation of cell-surface proteins leads to the exposure of terminal galactose residues, which can promote tumor metastasis and immune evasion by interacting with galectins. Therapeutic interventions include galectin inhibitors designed to treat fibrosis and various cancers by blocking these interactions. Furthermore, the asialoglycoprotein receptor (ASGPR) in the liver specifically recognizes and clears proteins bearing terminal galactose or N-acetylgalactosamine (GalNAc), a mechanism exploited for liver-targeted drug delivery. The galactosylation status of the Fc region of IgG antibodies also plays a vital role in modulating effector functions, such as complement-dependent cytotoxicity (CDC).

Other names

Cell-surface glycans with N-terminal galactoseTerminal galactoseAsialoglycansGalactose-terminated glycansGal-terminated N-glycansTerminal beta-galactose

Binding to terminal galactose residues to facilitate viral entry (AAV9), inhibit galectin-mediated signaling and lattice formation, or trigger receptor-mediated endocytosis via the asialoglycoprotein receptor (ASGPR).