Synthesis of homogeneous heparan sulfate proteoglycans

通过这一奖项，化学合成计划资助密歇根州立大学化学系的黄学飞教授建立了一种化学酶法合成含有均一硫酸乙酰肝素多聚糖的硫酸乙酰肝素肽多聚糖(HSPG)。该项目涉及与北卡罗来纳大学的刘健教授在酶方面的合作。HSPG参与多种生物学过程，如伤口愈合、癌症转移、细胞黏附、病毒感染和细胞增殖。然而，由于获得均一热休克蛋白的机会有限，特别是关于硫酸盐化的程度和位置，生物学研究受到了阻碍。糖肽将通过化学合成进行组装。然后，糖链将被延长，硫化反应将以不同的方式进行，以产生特定的硫酸乙酰肝素结构。化学合成和酶合成的结合创造了一种潜在的有效途径来获得这些复杂的糖结合物，这将为最终合成均一的硫酸乙酰肝素蛋白多糖奠定基础。该项目的更广泛的影响包括通过建立获得硫酸乙酰肝素(HS)肽多聚糖的新方法来促进糖结合化学的发展。具有明确的硫酸化程度和位置的HS肽聚糖的可获得性将通过提供机会来解开不同HS-肽聚糖的结构-功能关系，从而对化学生物学领域产生科学上更广泛的影响。研究活动将纳入教育、培训和社区外展。这一研究项目有望帮助建立下一代糖科医生的人才库，他们的需求量很大，特别是在复杂的寡糖和糖共轭合成这一困难和专门的领域。

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.