N-linked terminal galactose-containing glycan

N-linked terminal galactose-containing glycans are carbohydrate motifs found on the surface of various glycoproteins, characterized by a galactose residue at the non-reducing end of an N-linked oligosaccharide chain (Ashwell & Harford, 1982). While the target name mentions lipids, N-linked glycans are biochemically restricted to proteins, whereas lipids typically feature glycans attached via different linkages, such as those found in glycolipids (Pinho & Reis, 2015). These glycans are usually masked by terminal sialic acid residues, and their exposure, often termed desialylation, serves as a critical biological signal for protein clearance via the asialoglycoprotein receptor (ASGPR) in the liver and for binding by the galectin family of lectins (Rabinovich & Toscano, 2009). In pathological states like cancer, the aberrant exposure of these glycans facilitates the formation of pro-tumorigenic lattices that promote metastasis and immune evasion. Therapeutic approaches include galectin inhibitors like Belapectin to disrupt these interactions and sialidase-based therapies like E-602 to expose these glycans on tumor cells for immune recognition (Chalasani et al., 2020; Palleon Pharmaceuticals, 2023). Additionally, synthetic versions of these glycans are utilized in GalNAc-conjugate technologies to target therapeutic payloads to the liver via ASGPR-mediated endocytosis.

Other names

Terminal galactose glycansDesialylated N-glycansAsialoglycansGalactose-terminated N-linked glycansAsialoglycoproteins

Competitive inhibition of galectin binding; Enzymatic desialylation to expose terminal galactose; Facilitation of receptor-mediated endocytosis via ASGPR