Synthesis of multivalent chondroitin sulfate oligosaccharides targeting the exosites of cathepsin K
Résumé
Chondroitin sulfate (CS) are heteropolysaccharides that belong to a family of complex polyanionic polymers called glycosaminoglycans (GAGs). They consist of a repeating disaccharide unit composed of a D-glucuronic acid (D-GlcA) and 2-acetamindo-2-deoxy-D-galactose (D-GalNAc) and bearing sulfate groups primarily at the position 4 (CS-A) and/or position 6 (CS-E/CS-C) of the D-GalNAc [1]. Their structural diversity and sulfation patterns determine their biological functions, including neuronal development, morphogenesis, and cell-cell recognition, through interactions with various proteins [2]. Additionally, CS are major structural components of connective tissues, particularly in cartilage, skin, and bone [3]. Multivalency is a key feature in glycan-protein interactions, enhancing both affinity and specificity while enabling supramolecular organization at the cell surface [4]. Despite its importance, multivalent CS constructs remain scarce [5]. Here, we present our approach, for the synthesis of well-defined CS oligosaccharides with controlled sulfation [6] patterns and various linkage systems and platforms to promote multivalency.