LacNAc

N-acetyllactosamine, commonly abbreviated LacNAc, is a disaccharide composed of galactose linked beta-1,4 to N-acetylglucosamine (Galβ1-4GlcNAc). It is a widespread structural motif in vertebrate glycans and serves as the fundamental building block for longer repeats found on many glycoproteins and glycolipids.

In N-linked and O-linked glycans, LacNAc units are repeatedly added to extend glycan chains. The length and branching of LacNAc-containing chains contribute to substantial heterogeneity among glycoproteins and influence recognition by carbohydrate-binding proteins, including lectins and antibodies. Poly-N-acetyllactosamine chains, comprising repeating LacNAc units in alternating linkages, are common on diverse glycoconjugates and serve as extended platforms for interactions with lectins such as galectins.

Biosynthesis is driven by glycosyltransferases. The formation of LacNAc begins with beta-1,4-galactosyltransferases (B4GalTs) that add Gal to GlcNAc residues. Further chain elongation involves additional glycosyltransferases, including beta-1,3-N-acetylglucosaminyltransferases, which create the alternating repeat structure characteristic of poly-LacNAc. The exact length and composition of LacNAc-containing chains are regulated by cell type and physiological state.

Functionally, LacNAc motifs are notable ligands for galectins and other glycan-binding proteins, contributing to cell-cell adhesion, signaling, endocytosis, and immune modulation. Alterations in LacNAc length and density are observed in development and various diseases, including cancer and inflammatory conditions, and can affect pathogen binding to host glycans. In research, LacNAc serves as a key motif in glycomics analyses and glycoengineering efforts.