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 an integrated approach for the identification of ligands for HS-binding proteins employing affinity purification, sequencing of HS oligosaccharides by novel mass spectrometric approaches and the chemical synthesis of libraries of HS oligosaccharides for structure activity relationships. The methodology has been employed to identify ligands for the ROBO-1 which is a protein involved in cell signaling and development.

Integrated approach to uncover ligands for heparan sulfate binding proteins

249th National Meeting (2015)

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