• The nonreducing terminal GalNAc(β1-4)GlcNAc (LacdiNAc or LDN) group is found as part of N- and O-linked glycans of both vertebrate and invertebrate glycoproteins (PMID: 25003135). This structure is synthesized by two enzymes B4GALNT3 and B4GALNT4.
• LacdiNAc structures are less abundant compared to Type-II lactosamine chains and they have been reported on a limited number of proteins including pituitary prolactin, lutropin (LH), follitropin (FSH), glycodelin and Tissue Factor Pathway Inhibitors (TFPI). They are also formed in epithelial cells of kidney and breast origin.
• Enzyme activity may be peptide core specific suggesting biological importance of such modifications. Due to this peptide specificity the distribution of this substructure may also be limited.
• The β1,4-linked GalNAc can be further modified with a variety of moieties: 4-linked SO4, α2,6-Neu5Ac, or at the subterminal by α1,3-fuc. This results in additional epitopes like 4SGalNAc(β1-4)GlcNAcβ, Siaα(2-6)GalNAc(β1-4)GlcNAcβ, GalNAc(β1-4)[Fuc(α1-3)]GlcNAcβ etc.
• β4GalNAc-T3 and β4GalNAc-T4 transcripts are widely expressed. β4GalNAc-T3 transcript is most abundant in the stomach, colon, and testis. β4GalNAc-T4 transcript is abundant in the ovary, brain, colon, uterus, fetal brain, kidney, and lung.
• Wisteria floribunda agglutinin binds β-linked GalNAc, and is used to monitor B4GalNT3,4 activity in tissue sections.
• β4GalNAc-T3 is upregulated in 75 % of primary colon cancers, correlating with a more malignant phenotype. Enzyme activity related to LacdiNAc is also dysregulated during other cancers: ovarian, pancreatic, prostate and breast.