Profiling glycol-split heparins by high-performance liquid chromatography/mass spectrometry analysis of their heparinase-generated oligosaccharides.
Profiling glycol-split heparins by high-performance liquid chromatography/mass spectrometry analysis of their heparinase-generated oligosaccharides.
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DOI：
10.1016/j.ab.2012.11.011
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Naggi A
中科院分区：
文献类型：
--
作者：
Alekseeva A;Casu B;Torri G;Pierro S;Naggi A
乙二醇分裂（gs）肝素是由高碘酸氧化/硼氢化还原肝素得到的，目前用作抗凝血和抗血栓药物，在抗癌和抗炎症治疗中引起越来越多的兴趣。由于抗凝血酶III （AT）结合位点因乙二醇分裂而失活，导致抗凝血活性丧失，这些新的医疗用途受到青睐。肝素的结构尚未得到详细的研究。本研究将离子对反相色谱法（IPRP-HPLC）和电喷雾电离质谱法（ESI-MS）应用于猪粘膜肝素制备的gs-肝素酶消化产生的低聚糖分析。该方法也被发现非常有效地分析从不同动物和组织来源的肝素中获得的乙醇分裂衍生物。除了主要的2- o -硫酸双糖外，肝素酶酶切产物主要含有含有一个或两个gs残基的四糖和六糖，具有典型的单个gs-肝素分布模式。具有两个gs残基的七硫酸化单n -乙酰化六糖已被证明是肝素链中gs修饰的AT结合位点的标记。
Glycol-split (gs) heparins, obtained by periodate oxidation / borohydride reduction of heparin currently used as anticoagulant and antithrombotic drug, are arousing increasing interest in anti-cancer and anti-inflammation therapies. These new medical uses are favored by the loss of anticoagulant activity associated with glycol-splitting-induced inactivation of the antithrombin III (AT) binding site. The structure of gs-heparins has not been studied yet in detail. In this work, an ion-pair reversed-phase chromatography (IPRP-HPLC) coupled with electrospray ionization mass spectrometry (ESI-MS) widely used for unmodified heparin has been adapted to the analysis of oligosaccharides generated by digestion with heparinases of gs-heparins usually prepared from porcine mucosal heparin. The method has been also found very effective in analyzing glycol-split derivatives obtained from heparins of different animal and tissue origin. Besides the major 2-O-sulfated disaccharides, heparinase digests of gs-heparins mainly contain tetra- and hexasaccharides incorporating one or two gs residues, with distribution patterns typical for individual gs-heparins. A heptasulfated, mono-N-acetylated hexasaccharide with two gs residues has been shown to be a marker of the gs-modified AT binding site within heparin chains.
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影响因子：
6.9
作者：
Casu, Benito;Naggi, Annamaria;Torri, Giangiacomo
通讯作者：
Torri, Giangiacomo
影响因子：
2.9
作者：
BITTER, T;MUIR, HM
通讯作者：
MUIR, HM
影响因子：
6.7
作者：
Bisio, Antonella;Vecchietti, Davide;Torri, Giangiacomo
通讯作者：
Torri, Giangiacomo
影响因子：
5.7
作者：
Guerrini, Marco;Guglieri, Sara;Torri, Giangiacomo
通讯作者：
Torri, Giangiacomo
影响因子：
6.2
作者：
Bertini, S;Bisio, A;Terbojevich, M
通讯作者：
Terbojevich, M