Journal
CARBOHYDRATE POLYMERS
Volume 227, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2019.115312
Keywords
Low molecular weight heparin; Desulfation; Oligosaccharides; Inflammation; Structure-activity relationship
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Funding
- National Key RAMP
- D Program of China [2018YFA0902000]
- National Natural Science Foundation of China [21778076]
- 111 Project from the Ministry of Education of China the State Administration of Foreign Expert Affairs of China [111-2-07]
- PAPD of Jiangsu Province
- Double First-Class University project [CPU2018GY36]
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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.
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