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

被引：31

作者：

Shen, Xuemin ^{[1
]}

Liu, Zhenfeng ^{[2
]}

Li, Junhui ^{[1
]}

Wu, Dongmei ^{[1
]}

Zhu, Meng ^{[3
,4
]}

Yan, Lufeng ^{[1
]}

Mao, Guizhu ^{[1
]}

Ye, Xingqian ^{[1
]}

Linhardt, Robert J. ^{[5
]}

Chen, Shiguo ^{[1
]}

机构：

[1] Zhejiang Univ, Zhejiang Key Lab Agrofood Proc, Dept Food Sci & Nutr, Fuli Inst Food Sci, Hangzhou 310058, Zhejiang, Peoples R China

[2] Chiatai Qingchunbao Pharmaceut Co Ltd, Inst Hlth Prod, Hangzhou 310023, Zhejiang, Peoples R China

[3] Soochow Univ, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou 215021, Jiangsu, Peoples R China

[4] Soochow Univ, Coll Pharmaceut Sci, Suzhou 215021, Jiangsu, Peoples R China

[5] Rensselaer Polytech Inst, Ctr Biotechnol 8 Interdisciplinary Studies, Dept Chem & Chem Biol, Biotechnol Ctr 4005, Troy, NY 12180 USA

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES | 2019年 / 133卷

基金：

中国国家自然科学基金;

关键词：

Low molecular weight heparin; Radical reaction; Ultrasonic degradation; Anti-metastasis; DEGRADATION; DEPOLYMERIZATION; POLYSACCHARIDE; INHIBITION; KINETICS; CHITOSAN; SULFATE; CANCER; LMWH; SIZE;

D O I：

10.1016/j.ijbiomac.2019.04.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 [3-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 H202/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/Cu-2 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. (C) 2019 Elsevier B.V. All rights reserved.

引用

页码：101 / 109

页数：9

共 38 条

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