神经细胞再生障碍是制约中枢神经系统损伤疾病治愈的关键。硫酸软骨素(CS)在损伤后分泌量显著上调，对受损轴突有强烈再生调控作用，且不同结构CS表现出显著活性差异。限于结构复杂性及获得性困难，目前CS糖链与神经再生调控关系及详细机理研究难于深入。课题拟在前期研究基础上，以来源丰富、价廉且与CS结构相似的透明质酸（HA）为原料，通过酶及化学法选择性降解，高效获取HA四糖、二糖砌块，通过正交保护基引入、构型翻转、片段组装、羟基衍生化等步骤完成大小、硫酸化位点、数量不同、结构多样的CS寡糖库；通过活性评价及机理研究，总结构效关系，发现具有良好促进轴突再生活性的糖类先导物及探针，为进一步寻找治疗神经损伤药物打下基础。采用天然多糖降解、组装新策略构建CS寡糖库，快速解决获得性及多样性问题，开展CS与神经再生化学生物学及药物化学研究对于丰富糖胺聚糖合成化学、明晰神经再生调控机理、发展新的治疗药物具有重

The promotion of regeneration of neural cell axons is the key for the cure of spinal cord injury. The secretion of chondroitin sulfate (CS) is significantly up-regulated after the injury, and CS strongly regulates the regeneration of injured axons. Different sub-types of CS show significant differences in bioactivities. The complex CS structure and the difficulty to obtain enough CS hamper the current study on the role of CS in spinal cord injury. Based on the preliminary study, we intend to utilize hyaluronic acid, a CS like, low-cost and plentiful GAG (glycosaminoglycan), to efficiently produce di- and tetrasaccharides of Hyaluronic acid via selective enzymatic degradation and chemical hydrolysis, Furthermore, through modifying the di- and tetrasaccharides using functional group orthogonal protection, configuration conversion, building block assembly and hydroxyl group derivatization, we intend to oligosaccharide build molecular libraries of CS that have diverse molecular weights, number of sulfate groups and sulfated positions. We are going to evaluate the bioactivities of the diverse compounds, study their action mechanisms, and reveal the structure activity relationships (SARs). These efforts should allow us to discover the lead compounds that strongly promote the axon regeneration. The results of this study would set the foundation for further discovering novel drugs for the treatment of spinal cord injury. Quick access to diverse structures of CS can be achieved by utilizing a strategy that includes selective degradation of natural polysaccharides and novel assembling methods. Conducting chemical biology and medicinal chemistry study on CS and axonal regeneration can enrich the chemical synthesis techniques of GAG, reveal the regulation mechanisms on axonal regeneration, and identify targets for the development of novel drugs.