The components and activities analysis of a novel anticoagulant candidate dHG-5
The components and activities analysis of a novel anticoagulant candidate dHG-5
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新型抗凝候选药物 dHG-5 的成分和活性分析。
DOI：
10.1016/j.ejmech.2020.112796
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发表时间：
2020-12-01
影响因子：
6.7
通讯作者：
Zhao, Jinhua
中科院分区：
文献类型：
--
作者：
Sun, Huifang;Gao, Na;Zhao, Jinhua
内在Xase （iXase）是内在凝血途径中最后一个也是限速的酶复合物，可能是抗血栓治疗的理想靶点。从海参Holothuria fuscopunctata提取的聚焦糖胺聚糖解聚部分dHG-5 （Mw 5.2 kDa）显示出对iXase的有效选择性抑制（IC50, 14 nM）。本研究纯化了dHG-5中所含的一系列低聚糖，并通过二维核磁共振和质谱证实了它们的精确结构。抗ixase、fixa结合、抗凝血和抗血栓活性(y)与分子量(x)之间的关系可以近似表示为幂函数（y = a x x(b)）， dHG-5的这些活性大约等于其低聚糖的加权平均和。由于dHG-5具有突出的药理学性质、明确的化学成分和可解释的低聚糖与dHG-5之间的药理行为关系，dHG-5有望成为一种理想的新型抗凝药物。(C) 2020 Elsevier Masson SAS。版权所有。
Intrinsic Xase (iXase), the last and rate-limiting enzyme complex in the intrinsic coagulation pathway, may be an ideal target for antithrombotic treatment. A depolymerized fraction of fucosylated glycosaminoglycan from sea cucumber Holothuria fuscopunctata, dHG-5 (Mw 5.2 kDa), showed potent and selective inhibition of iXase (IC50, 14 nM). In this work, the series of oligosaccharides contained in dHG-5 were purified and their precise structures were confirmed by 2D NMR and MS spectra. The relationships between anti-iXase, f.IXa-binding, anticoagulant and antithrombotic activities (y) and molecular weight (x) could be approximately expressed as the power function (y = a x x(b)), and these activity potencies of dHG-5 were approximately equivalent to the weighted average sum of that of its oligosaccharides. Given the prominent pharmacological properties, well-defined chemical composition and explicable relationships between dHG-5 and its oligosaccharides in pharmacological behaviors, dHG-5 is expected to be an ideal novel anticoagulant medicine. (C) 2020 Elsevier Masson SAS. All rights reserved.