Synthesis of a chondroitin sulfate disaccharide library and a GAG-binding protein interaction analysis.

Chondroitin sulfate (CS), which belongs to the glycosaminoglycan (GAG) superfamily, is a linear sulfated polysaccharide involved in various biological processes. CS structure is very heterogeneous and contains various sulfation patterns owing to the multiple and random enzymatic modifications that occur during its biosynthesis. The resultant microdomain structure in the CS chain interacts with specific biomolecules to regulate biological functions.

Syntheses of chondroitin sulfate tetrasaccharide structures containing 4,6-disulfate patterns and analysis of their interaction with glycosaminoglycan-binding protein.

Chondroitin sulfate tetrasaccharide ligand conjugates, namely GlcA-GalNAc6S-GlcA-GalNAc4S6S (CS-C+E) 1, GlcA2S-GalNAc6S-GlcA2S-GalNAc4S6S (CS-D+T) 2, GlcA-GalNAc4S6S-GlcA-GalNAc4S (CS-E+A) 3, GlcA-GalNAc4S6S-GlcA-GalNAc6S (CS-E+C) 4, and GlcA-GalNAc4S6S-GlcA-GalNAc4S6S (CS-E+E) 5, were systematically synthesized using a disaccharide building block 6. Synthesized CS tetrasaccharide structures were immobilized onto gold-coated chips to prepare array-type sugar chips, and the binding properties of protein were evaluated by surface plasmon resonance imaging biosensor. CS-D+T, CS-E+A, CS-E+C, and CS-E+E showed greater affinity for basic fibroblast growth factor than did other tetrasaccharides (CS-C+D, C+E, D+D).