State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
Carbohydr Polym. 2020 Jan 1;227:115312. doi: 10.1016/j.carbpol.2019.115312. Epub 2019 Sep 12.
Low molecular weight heparin (LMWH) possesses a dual function of anticoagulation and anti-inflammation. While the structures and mechanisms on its anticoagulation have been widely studied, the structural features responsible for the anti-inflammatory activity of LMWH remain to be explored. In the present study, guided by an anti-inflammation assay, a non-anticoagulant species was generated from partial desulfation of LMWH to fully retain the anti-inflammatory activity, from which five fractions were further separated and three of them were characterized by enzymatic degradation, hydrophobic labeling, C18-based HPLC and LC-MS/MS analyses. The structure-activity relationship revealed that the sulfate groups in LMWH are critical to distinguish and separate the activities of anticoagulation and anti-inflammation, leading to the identification of a synthetic heparosan-type heptasaccharide as a potent anti-inflammatory agent. The present strategy enables the simplification of complex polysaccharides to bioactive synthetic oligosaccharides for therapeutic utility.
低分子量肝素 (LMWH) 具有抗凝和抗炎的双重功能。尽管其抗凝作用的结构和机制已得到广泛研究，但 LMWH 抗炎活性的结构特征仍有待探索。在本研究中，通过抗炎测定指导，从 LMWH 的部分脱硫生成一种非抗凝物质，以完全保留抗炎活性，从中进一步分离出五个馏分，其中三个通过酶降解、疏水性标记、C18 反相 HPLC 和 LC-MS/MS 分析进行了表征。结构-活性关系表明，LMWH 中的硫酸基团对于区分和分离抗凝和抗炎活性至关重要，从而鉴定出一种合成的肝素聚糖型七糖作为有效的抗炎剂。本策略能够简化复杂多糖为具有治疗用途的生物活性合成寡糖。
