GalGalNAc

GalGalNAc is a disaccharide comprising galactose (Gal) linked β1-3 to N-acetylgalactosamine (GalNAc). In the context of protein glycosylation, this disaccharide forms the core 1 O-glycan when attached to serine or threonine residues, producing the Thomsen-Friedenreich antigen, often written as Galβ1-3GalNAcα1-Ser/Thr. This core disaccharide serves as a scaffold for further elaboration into a broad family of mucin-type O-glycans.

Biosynthesis begins with the transfer of GalNAc to Ser/Thr by polypeptide N-acetylgalactosaminyltransferases (ppGalNAcTs), forming the Tn antigen (GalNAcα1-Ser/Thr). The core 1 synthase (C1GALT1), with its molecular chaperone COSMC, then adds a galactose in β1-3 linkage to the GalNAc, yielding Galβ1-3GalNAcα1-Ser/Thr. Subsequent modifications, such as sialylation and fucosylation, generate a variety of longer O-glycan structures.

Functional and clinical notes: the Galβ1-3GalNAc core is a common motif in mucin-type glycoproteins and influences protein stability, folding, and cell surface interactions. The exposed T antigen and related structures are recognized by specific lectins and can be altered in disease. In cancer, changes in O-glycosylation often lead to altered expression of Tn/T antigens and the core 1 structure, providing potential biomarkers and immunogenic targets.

Synonyms for the motif include the core 1 disaccharide and Galβ1-3GalNAc, frequently described as the T antigen precursor.