Synthesis of homogeneous heparan sulfate proteoglycans

Michigan State University, East Lansing MI

Investigators

Abstract

With this award, the Chemical Synthesis Program is funding Professor Xuefei Huang of the Department of Chemistry at Michigan State University to establish a chemoenzymatic method to synthesize heparan sulfate peptidoglycans (HSPG's) containing homogeneous heparan sulfate glycans. The project involves a collaboration on the enzymatic side with Professor Jian Liu at the University of North Carolina. HSPG's are implicated in biological processes as diverse as wound healing, cancer metastasis, cell adhesion, viral infection and cell proliferation. Yet biological studies have been hampered by limited access to homogeneous HSPGs, particularly with regard to the extent and position of sulfation. The glycopeptides will be assembled through chemical synthesis. The glycan chains will then be extended and the sulfations performed enzymatically to create specific heparan sulfate structures in a divergent manner. The interfacing of chemical and enzymatic synthesis creates a potentially powerful approach to access these complex glycoconjugates which will lay the foundation for the eventual synthesis of homogeneous heparan sulfate proteoglycans. The Broader Impacts of this project involve the advancement of glycoconjugate chemistry by establishing new methods to access heparan sulfate (HS) peptidoglycans. The availability of HS peptidoglycans with both a well-defined degree and position of sulfation should have a scientific broader impact on the field of chemical biology, by providing opportunities to unravel structure-function relationships for distinct HS-peptidoglycans. The research activities will be incorporated into education, training and community outreach. This research project is expected to help build the talent pool of next generation glycoscientists, who are in high demand especially in the difficult and specialized field of complex oligosaccharide and glycoconjugate synthesis.