Although hundreds of heparan sulfate binding proteins have been identified, and implicated in a myriad of physiological and pathological processes, very little information is known about ligand requirements for binding and mediating biological activities by these proteins. This difficulty results from a lack of technology for establishing structure-activity-relationships, which in turn is due to the structural complexity of natural HS and difficulties of preparing well-defined HS-oligosaccharides. To address this deficiency, we have developed a modular approach for the parallel combinatorial synthesis of HS oligosaccharides that utilizes a relatively small number of selectively protected disaccharide building blocks, which can easily be converted into glycosyl donors and acceptors. The modular building blocks have been used for the preparation of a library of oligosaccharides, which has been employed to probe ligand requirements of several HS-binding proteins. To facilitate high through put screening, spacer modified HS-oligosaccharides have been employed for microarray fabrication.

Identification of ligands for chemokines and cytokines using a heparan sulfate microarray

245th National Meeting (2013)

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