Figure 4

Illustration of phosphorylated (phosphated) and sulfated (sulfurylated) glycan “words”. 6-Phosphorylation of a mannose moiety (in the context of a mannose-rich pentasaccharide) is the key section of a routing signal in lysosomal enzymes (a), 4-sulfation of the GalNAcβ1,4GlcNAc (LacdiNAc) epitope forms the “postal code” for clearance from circulation by hepatic endothelial cells of pituitary glycoprotein hormones labeled in such a way (b), the HNK-1 (human natural killer-1) epitope (3-sulfated GlcAβ1,3Galβ1,4GlcNAc) is involved in cell adhesion/migration in the nervous system (c) and the encircled 3-O-sulfation in the pentasaccharide’s center is essential for heparin’s anti-coagulant activity (d). All sugars are in their pyranose form. Please note that the central glucosamine unit has N,O-trisulfation and that the 2-sulfated IdoA, given in the ¹C₄ conformation, can also adopt the hinge-like ²S_O skew-boat structure (please see Figure 3; about 60% or more for the ²S_O form in equilibrium depending on the structural context) when present within glycosaminoglycan chains of the proteoglycan heparin. 2-Sulfation of IdoA serves two purposes: favoring the hinge-like ²S_O conformation and precluding re-conversion to GlcA (from [1], with permission).