Synthesis of homogeneous heparan sulfate proteoglycans

均质硫酸乙酰肝素蛋白聚糖的合成

• 批准号: 1111550
• 负责人: Xuefei Huang
• 金额: $ 39万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1111550&HistoricalAwards=false
• 关键词: Synthesis; homogeneous; heparan; sulfate; proteoglycans

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.

有了这个奖项，化学合成计划正在资助密歇根州立大学化学系的黄雪飞教授建立一种化学酶法来合成含有均匀硫酸乙酰肝素聚糖的硫酸乙酰肝素肽聚糖（HSPG）。 该项目涉及与北卡罗来纳州大学的Jian Liu教授在酶方面的合作。 HSPG涉及多种生物过程，如伤口愈合、癌症转移、细胞粘附、病毒感染和细胞增殖。 然而，生物学研究一直受到限制，获得同质HSPG，特别是在硫酸化的程度和位置。糖肽将通过化学合成组装。 然后聚糖链将被延长，并且通过酶促进行硫酸化，以不同的方式产生特定的硫酸乙酰肝素结构。 化学合成和酶促合成的结合为获得这些复杂的糖缀合物创造了一个潜在的强有力的方法，这将为最终合成均匀的硫酸乙酰肝素蛋白聚糖奠定基础。该项目的更广泛影响包括通过建立新的方法来获得硫酸乙酰肝素（HS）肽聚糖，从而促进糖缀合物化学的发展。 具有明确定义的硫酸化程度和位置的HS肽聚糖的可用性应该对化学生物学领域产生更广泛的科学影响，通过提供解开不同HS-肽聚糖的结构-功能关系的机会。 研究活动将纳入教育、培训和社区外联活动。 该研究项目预计将有助于建立下一代糖科学家的人才库，特别是在复杂寡糖和糖缀合物合成的困难和专业领域。