IdoA2S

IdoA2S, short for 2-O-sulfated iduronic acid, is a modified monosaccharide unit found in certain glycosaminoglycans (GAGs). It consists of iduronic acid (IdoA) bearing a sulfate group at the 2-position. IdoA2S occurs predominantly in dermatan sulfate and in the heparin/heparan sulfate family of GAGs and contributes to their functional diversity.

Biosynthesis of IdoA2S involves two enzymatic steps. First, glucuronic acid (GlcA) residues in the polysaccharide chain are epimerized to iduronic acid by a C5-epimerase. Subsequently, 2-O-sulfotransferases add sulfate to the 2-O position of IdoA, generating IdoA2S within the chain. The content of IdoA2S varies with tissue type and GAG class, influencing the properties of the polysaccharide.

Structural and functional significance of IdoA2S stems from its effect on the conformation and flexibility of iduronic acid residues. The presence of the 2-O-sulfate can stabilize conformations that enable tight, specific interactions with a range of proteins. In heparin-derived sequences, IdoA2S-containing motifs contribute to high-affinity binding to antithrombin III and to anticoagulant activity. Beyond anticoagulation, IdoA2S modulates interactions with growth factors, chemokines, enzymes, and extracellular matrix components, influencing processes such as coagulation, cell signaling, and matrix organization.

Analytical approaches to IdoA2S include disaccharide composition analysis after selective enzymatic digestion, often coupled with mass spectrometry or chromatography, as well as spectroscopic methods like NMR to identify 2-O-sulfated iduronic acid residues. Understanding IdoA2S distribution aids in elucidating structure–function relationships in glycosaminoglycans.