2. Academic Validation
  3. The components and activities analysis of a novel anticoagulant candidate dHG-5

The components and activities analysis of a novel anticoagulant candidate dHG-5

  • Eur J Med Chem. 2020 Dec 1;207:112796. doi: 10.1016/j.ejmech.2020.112796.
Huifang Sun 1,  Na Gao 2,  Lin Ren 3,  Shuang Liu 1,  Lisha Lin 1,  Wenqi Zheng 2,  Lutan Zhou 1,  Ronghua Yin 3,  Jinhua Zhao 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 2 School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, China.
  • 3 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
  • 4 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China; School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, China. Electronic address: zhao.jinhua@yahoo.com.
PMID: 32942073 DOI: 10.1016/j.ejmech.2020.112796
Abstract

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 × xb), 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.

Keywords

Anticoagulation; Antithrombosis; FG oligosaccharides; dHG-5; iXase inhibitor.

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