Terminal N-acetylgalactosamine-terminated glycans (GalNAc-glycans)

Terminal N-acetylgalactosamine (GalNAc)-terminated glycans, including those structurally related to the LacdiNAc (GalNAcβ1-4GlcNAc) motif, represent a significant class of carbohydrate structures involved in biological signaling and disease pathology (Cummings & Nyame, 1999). These glycans are critical for the rapid clearance of glycoproteins, such as luteinizing hormone, from the circulation via specific hepatic receptors that recognize terminal GalNAc or sulfated GalNAc residues (Fiete et al., 1991). In the context of oncology, these structures often function as tumor-associated carbohydrate antigens (TACAs) and are upregulated in various malignancies, including breast, ovarian, and prostate cancers (Dell et al., 2010). They serve as ligands for the Macrophage Galactose-type Lectin (MGL/CD301), an interaction that can lead to the suppression of anti-tumor immune responses by inducing a tolerogenic phenotype in dendritic cells (van Vliet et al., 2008). Therapeutic targeting of these glycans or their cognate receptors is an active area of research, focusing on restoring immune surveillance or utilizing the glycans as biomarkers for diagnostic imaging and patient stratification (Micklem et al., 2020). Additionally, these glycans are prominent on the surface of certain helminth parasites, where they play a role in host-parasite interactions and immune evasion (Nyame et al., 2004). Furthermore, GalNAc-conjugated RNA therapeutics leverage the high affinity of terminal GalNAc for the asialoglycoprotein receptor to achieve liver-specific drug delivery (Nair et al., 2014).

Other names

Other terminal GalNAc-terminated glycans structurally related to LacdiNAcLacdiNAc-related glycansLDN-related structuresTerminal GalNAc oligosaccharidesGalNAc-terminated glycans

Targeted delivery to the liver via the asialoglycoprotein receptor (ASGPR) or modulation of immune signaling via MGL binding