An important modification is the epimerization of GlcA residues to IdoA residues by C-5 inversion at the polymer level of a (β-GlcA-1,3-β-GalNAc-1,4-)n substrate (Fig. 1B) 4. Individual saccharide units in CS/DS can exist in different conformations depending on their structural arrangement. IdoA residues allow flexibility given their ability to switch between 1C4 (chair), 2S0 (skew boat) and 4C1 (chair) conformations (Fig. 1C), whereas GlcA residues are less flexible and exist in the 4C1 (chair) conformation 5. IdoA can occur in three different arrangements: (a) as a single IdoA-containing disaccharide surrounded by GlcA containing disaccharides; (b) in structures where they alternate with GlcA containing disaccharides or (c) in long blocks of adjacent IdoA-containing disaccharides (Fig. 1A). The sulfation pattern differs according to the IdoA distribution because IdoA blocks are mainly 4-sulfated with some adjacent sulfated IdoA residues (iB) close to the nonreducing terminal of the blocks 6,7. The short GlcA blocks are mostly 4-sulfated, whereas longer blocks also contain 6-sulfated GalNac residues 8. The resulting CS/DS chains therefore contain different domains that enrich their functional properties. The presence of alternating IdoA-GlcA
