Preparation of low molecular weight heparin using an ultrasound-assisted Fenton-system
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Authors
Zhi, Zijian
Li, Junhui
Chen, Jianle
Li, Shan
Cheng, Huan
Liu, Donghong
Ye, Xingqian
Linhardt, Robert J.
Chen, Shiguo
Issue Date
2019-04-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Heparin, a high-molecular weight acidic polysaccharide, has raised much interest in the field of biomedical research due to its multiple bio-functions. The anticoagulant application of heparin in routine clinical practice, however, has been limited as the large molecular size of heparin can reduce its subcutaneous bioavailability and lead to severe adverse consequences such as thrombocytopenia. Here, we report a highly efficient and convenient method to depolymerize high-molecular weight, unfractionated heparin (UFH), into low molecular weight heparin (LMWH) by combining physical ultrasonic treatment with the chemical Fenton reaction, referred to as sono-Fenton. We found that this combination treatment synergistically degraded UFH into a LMWH of 4.87 kDa within 20 min. We characterized the mechanism of sono-Fenton heparin degradation through multiple approaches, including HPLC-SAX, disaccharide composition, FT-IR, NMR and top-down analysis, and found that the uronic acid residue in heparin was the most susceptible site attacked by OH radicals produced in the sono-Fenton process. Importantly, the LMWH prepared by this method had significantly higher anticoagulant activity than UFH and other LMWHs. This approach represents an effective method to produce heparin with improved activity and should be potentially useful for heparin production in the pharmaceutical industry.
Description
Ultrasonics Sonochemistry, 52, 184–192
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Preparation of low molecular weight heparin using an ultrasound-assisted Fenton-system, Z. Zhi, J. Li, J. Chen, S. Li, H. Cheng, D. Liu, X. Ye, R. J. Linhardt, S. Chen, Ultrasonics Sonochemistry, 52, 184–192, 2019.
Publisher
Elsevier
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
18732828
13504177
13504177