Ramadan Sherif, Li Tianlu, Yang Weizhun, Zhang Jicheng, Rashidijahanabad Zahra, Tan Zibin, Parameswaran Narayanan, Huang Xuefei
Department of Chemistry, Michigan State University, 578 South Shaw Lane, East Lansing, Michigan 48824, United States.
Chemistry Department, Faculty of Science, Benha University, Benha, Qaliobiya 13518, Egypt.
ACS Cent Sci. 2020 Jun 24;6(6):913-920. doi: 10.1021/acscentsci.9b01199. Epub 2020 Jun 1.
Bikunin, a chondroitin sulfate (CS) proteoglycan clinically used to treat acute inflammation and sepsis, contains a CS chain with more than 20 monosaccharide units. To understand the function of the CS chain of bikunin, synthesis of long CS chains is needed. After exploring multiple glycosylation approaches and protective group chemistry, we report herein the successful generation of the longest CS chain to date (24-mer) in an excellent overall yield on a multi-mg scale. The anti-inflammatory activities of both bikunin and the synthetic 24-mer were determined, and the results demonstrate that both the glycan and the core protein are important for anti-inflammatory activities of bikunin by reducing macrophage production of proinflammatory cytokines.
比库宁是一种临床上用于治疗急性炎症和败血症的硫酸软骨素（CS）蛋白聚糖，其含有一条由20多个单糖单元组成的CS链。为了解比库宁CS链的功能，需要合成长CS链。在探索了多种糖基化方法和保护基化学后，我们在此报告，成功地以多毫克规模、优异的总收率生成了迄今为止最长的CS链（24聚体）。测定了比库宁和合成的24聚体的抗炎活性，结果表明，聚糖和核心蛋白通过减少巨噬细胞促炎细胞因子的产生，对比库宁的抗炎活性都很重要。
