Distribution, biosynthesis, recognition, identification and biological functions of LacdiNAc structures on N- and O-...

LacdiNAc (GalNAcβ1 → 4GlcNAc), a disaccharide structure on N- and O-glycans of glycoproteins, represents an important form of glycosylation modification. Several reviews have summarized the expression and biological significance of LacdiNAc glycans in human tumors. However, a comprehensive understanding of LacdiNAc glycans remains insufficient. In this review, we summarize the progress in research regarding distribution, biosynthesis, recognition and identification of LacdiNAc structures on N- and O-glycans in many different organisms, and discuss their critical biological functions. Studies have demonstrated that LacdiNAc glycans are widely expressed across diverse organisms, with significant variations in expression levels among species, organs, and cell types. LacdiNAc moieties and their sulfated, sialylated, and/or fucosylated forms can be recognized by specific receptors and lectins. The LacdiNAc structures on released glycans were mainly identified by MS-based glycomics and NMR. More recently, newly developed glycoproteomic methods and associated software have further facilitated site-specific and large-scale identification of LacdiNAc-containing glycopeptides. Consistent with their differential distribution, LacdiNAc glycans are involved in various biological processes, including hormone regulation, immune response mediation, cell growth and differentiation, as well as cancer development.