Identification of a heparosan heptasaccharide as an effective anti-inflammatory agent by partial desulfation of low molecular weight heparin
Identification of a heparosan heptasaccharide as an effective anti-inflammatory agent by partial desulfation of low molecular weight heparin
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通过低分子量肝素部分脱硫鉴定肝素七糖作为有效的抗炎剂
DOI：
10.1016/j.carbpol.2019.115312
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发表时间：
2020-01-01
影响因子：
11.2
通讯作者：
Chen, Yijun
中科院分区：
文献类型：
--
作者：
Pan, Qi;Zhang, Chengchang;Chen, Yijun
低分子量肝素（LMWH）具有抗凝和抗炎双重作用。虽然其抗凝作用的结构和机制已被广泛研究，但负责抗炎活性的LMWH的结构特征仍有待探索。在本研究中，通过抗炎试验的指导下，从LMWH的部分脱水产生一个非抗凝物质，以完全保留抗炎活性，从其中进一步分离出5个级分，并通过酶降解，疏水标记，基于C18的HPLC和LC-MS/MS分析对其中的3个进行表征。结构-活性关系表明，硫酸基团的LMWH是至关重要的，区分和分离的抗凝和抗炎活性，导致合成肝素型七糖作为一种有效的抗炎剂的鉴定。本发明的策略使得能够将复杂多糖简化为用于治疗用途的生物活性合成寡糖。
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.