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低分子肝素结构分析

发表时间:2015-02-15  浏览量:2712  下载量:1372
全部作者: 王章杰,徐晓晖,李道远,迟连利
作者单位: 山东大学国家糖工程技术研究中心
摘 要: 低分子肝素(low molecular weight heparin,LMWH)是肝素经化学方法或酶法降解制备而成的新型抗血栓药物。研究开发了系统的糖链指纹图谱分析方法。离子对反相色谱与质谱(reversed-phase ion-pairing liquid chromatography mass spectrometry,RPIP-LC-MS)联用技术分析完整糖链,成功检测到依诺肝素钠从四糖到二十六糖的36种主要组分。RPIP-LC-MS分析部分酶解产物,成功检测到依诺肝素钠部分降解产物中从二糖到十糖的65种主要组分。LMWH完全降解产物应用RPIP-LC-MS并结合柱前衍生可用于分析LMWH完全降解产物的各个组分。除8种常见肝素二糖以外,成功检测到依诺肝素钠完全降解产物中的末端修饰结构、3-O-硫酸四糖和三糖。
关 键 词: 分析化学;低分子肝素;离子对反相色谱与质谱联用;完整糖链;部分降解;完全降解
Title: Structural analysis of low molecular weight heparins
Author: WANG Zhangjie, XU Xiaohui, LI Daoyuan, CHI Lianli
Organization: National Glycoengineering Research Center, Shandong University
Abstract: Low molecular weight heparins (LMWH) are novel antithrombotic drugs prepared by either enzymatic or chemical depolymerization of heparin. In this study, systematic methodologies for fingerprinting analysis of LMWH were established. Reversed-phase ion-pairing liquid chromatography mass spectrometry (RPIP-LC-MS) approach revealed 36 components ranging from tetrasaccharides to hexacosasaccharides from enoxaparin. The partial digested fragments of enoxaparin was also analyzed using technique of RPIP-LC-MS. A total of 65 components from disaccharides to decasaccharides were characterized. RPIP-LC-MS coupled with pre-column derivatization was applied to analyze the exhaustive digests of enoxaparin. Besides the 8 natural common heparin disaccharides, many characteristic structures from enoxaparin, such as modified structures from both termini as well as 3-O-sulfated tetrasaccharides and trisaccharides, had been unambiguously identified.
Key words: analytical chemistry; low molecular weight heparin; reversed-phase ion-pairing liquid chromatography mass spectrometry; intact chain; partial digestion; exhaustive digestion
发表期数: 2015年2月第3期
引用格式: 王章杰,徐晓晖,李道远,等. 低分子肝素结构分析 [J]. 中国科技论文在线精品论文,2015,8(3):278-284.
 
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