Core 2 O-glycan (C2-O-glycan)

Core 2 O-glycans are a specific class of mucin-type O-linked oligosaccharides characterized by a β1-6 linkage of N-acetylglucosamine to the GalNAc residue of the Core 1 structure [1, 6]. These glycans are synthesized by the Core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT) family of enzymes and serve as critical scaffolds for the presentation of functional epitopes, such as sialyl Lewis X [1, 3]. Biologically, they play a fundamental role in cell-cell adhesion and leukocyte trafficking by acting as ligands for E-, P-, and L-selectins, which are essential for immune cell recruitment to sites of inflammation [1, 9]. In disease states, particularly cancer, the overexpression of Core 2 O-glycans is associated with increased metastatic potential, immune evasion, and poor prognosis, as they can mask peptide epitopes or facilitate tumor cell extravasation [1, 3, 5]. Consequently, Core 2 O-glycans and the enzymes responsible for their synthesis are significant therapeutic targets [2, 11]. Current drug development efforts include monoclonal antibodies and antibody-drug conjugates (ADCs) such as Ensituximab and PB-223 that specifically recognize these glycans as tumor-associated carbohydrate antigens (TACAs) [7].

Other names

Core 2 branched O-glycanCore 2 mucin-type O-glycanGalβ1-3(GlcNAcβ1-6)GalNAcCore 2 O-linked glycan

Monoclonal antibody binding to tumor-associated carbohydrate antigens; Inhibition of core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT) activity; Disruption of selectin-ligand interactions