Development of low molecular weight heparin by H2O2/ascorbic acid with ultrasonic power and its anti-metastasis property

Shen, Xuemin
Liu, Zhenfeng
Li, Junhui
Wu, Dongmei
Zhu, Meng
Yan, Lufeng
Mao, Guizhu
Ye, Xingqian
Linhardt, Robert J.
Chen, Shiguo
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Development of low molecular weight heparin by H2O2/ascorbic acid with ultrasonic power and its anti-metastasis property, X. Shen, Z. Liu, J. Li, D. Wu, M. Zhu, L. Yan, G. Mao, X. Ye, R.J. Linhardt, S. Chen, International Journal of Biological Macromolecules, 133, 101–109, 2019.
Low molecular weight heparins (LMWHs) are currently used as an anticoagulant agent since unfractionated heparin (UFH) can cause serious adverse drug reactions. LMWHs are commercially prepared using different methods such as nitrous acid cleavage and β-elimination under strong reaction conditions or with harsh chemicals, which may cause the saccharide units within the polysaccharide backbone to be decomposed and noticeably modified. This study demonstrates an effective method for depolymerizing heparin via the production of large amounts of free radicals from H2O2/ascorbic acid and ultrasonic power; this results in highly pure products because ascorbic acid can decompose during the reaction, which is different from the previously reported H2O2/Cu2+ method. The reaction conditions-including concentration of ascorbic acid, reaction temperature and intensity of ultrasonic power-were investigated and optimized. We found that the degradation behavior of heparin in this combined physicochemical process conformed to first-order reaction kinetics. The chemical composition and structures of different LMWHs were analyzed. The results showed the primary structure and sulfate esters were well preserved after the depolymerization, the major repeat units are (1-4)-linked glucosamine and iduronic acid. The further in vitro assays indicated that the LMWHs produced by H2O2/ascorbic acid with ultrasonic power have an anti-metastatic effect in A549 cells, which suggested the LMWHs rapidly prepared in this physicochemical way have a potential for anti-tumor metastatic function.
International Journal of Biological Macromolecules, 133, 101–109
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
International Journal of Biological Macromolecules