Structure and anticoagulant activity of sulfated galactans -: Isolation of a unique sulfated galactan from the red algae Botryocladia occidentalis and comparison of its anticoagulant action wtth that of sulfated galactans from invertebrates

Structure and anticoagulant activity of sulfated galactans -: Isolation of a unique sulfated galactan from the red algae Botryocladia occidentalis and comparison of its anticoagulant action wtth that of sulfated galactans from invertebrates
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DOI:
10.1074/jbc.m002422200
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发表时间:
2000-09-22
影响因子:
4.8
通讯作者:
Mourao, PAS
Mourao, PAS
中科院分区:
生物学2区
文献类型:
--
作者:
Farias, WRL;Valente, AP;Mourao, PAS

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我们的特点是硫酸化的D-半乳聚糖从红藻Botryocladia occurentalis的结构。发现该多糖具有以下重复结构(-4-α-D-Galp-1-->3-β-D-Galp-1-->),但具有可变的硫酸化模式。显然,总α-单元的三分之一是2,3-二-O-硫酸化的,另外三分之一是2-O-硫酸化的。由于抗凝血酶和/或肝素辅因子II对凝血酶和因子Xa的抑制增强,藻硫酸化D-半乳聚糖具有有效的抗凝血活性(与未分级肝素类似的效力)。我们还将实验扩展到几种来自海洋无脊椎动物的具有简单结构的硫酸多糖,其由单一重复结构组成。当与藻类硫酸化D-半乳聚糖的有效作用相比时,2-O-或3-O-硫酸化L-半乳聚糖以及S-O-硫酸化L-岩藻聚糖具有弱的抗凝作用。可能地,将两个硫酸酯添加到单个α-半乳糖残基上对抗凝作用具有“放大效应”,这不能完全归因于聚合物的电荷密度增加。这些结果表明,广泛的多样性的多糖从海洋鱼类和无脊椎动物是一个有用的工具,以阐明结构/抗凝活性的关系。
We have characterized the structure of a sulfated D-galactan from the red algae Botryocladia occidentalis. The following repeating structure (-4-alpha-D-Galp-1-->3-beta-D-Galp-1-->) was found for this polysaccharide, but with a variable sulfation pattern. Clearly one-third of the total alpha-units are 2,3-di-O-sulfated and another one-third are 2-O-sulfated, The algal sulfated D-galactan has a potent anticoagulant activity (similar potency as unfractionated heparin) due to enhanced inhibition of thrombin and factor Xa by antithrombin and/or heparin cofactor II. We also extended the experiments to several sulfated polysaccharides from marine invertebrates with simple structures, composed of a single repeating structure. A 2-O- or 3-O-sulfated L-galactan las well as a S-O-sulfated L-fucan) has a weak anticoagulant action when compared with the potent action of the algal sulfated D-galactan. Possibly, the addition of two sulfate esters to a single alpha-galactose residue has an "amplifying effect" on the anticoagulant action, which cannot be totally ascribed to the increased charge density of the polymer. These results indicate that the wide diversity of polysaccharides from marine alga and invertebrates is a useful tool to elucidate structure/anticoagulant activity relationships.