Mingyi Wu

Precise structures of fucosylated glycosaminoglycan and its oligosaccharides as novel intrinsic factor Xase inhibitors

Publisher: Elsevier BV

Date: 03-2018

DOI: 10.1016/J.EJMECH.2018.02.047

Abstract: Selective inhibition of the endogenous coagulation pathway is a promising strategy for developing new anticoagulants. Fucosylated glycosaminoglycan (FG), a structurally complex glycosaminoglycan, has distinct anticoagulant properties, especially the strong intrinsic factor Xase inhibitory activity that is recognized as a new target with potential physiological and therapeutic applications. Detailed knowledge of FG structures is necessary for developing a clinically effective intrinsic FXase inhibitor. However, challenges remain to elucidate FG structures as a basis for pharmaceutical development. Herein, using the highly selective β-elimination method, oligosaccharides with regular structures were prepared from the depolymerization products. Analysis of oligosaccharides further confirmed the precise structural sequence of the FG. Furthermore, biological activity assay suggested that these pure homogeneous oligosaccharides, particularly an octasaccharide, exhibit strong inhibition of the intrinsic coagulation pathway by inhibiting human intrinsic factor Xase. Our finding is significant for discovery of a new class of anticoagulant agents as intrinsic factor Xase inhibitors.

Modulating the degree of fucosylation of fucosylated chondroitin sulfate enhances heparin cofactor II-dependent thrombin inhibition

Publisher: Elsevier BV

Date: 06-2018

DOI: 10.1016/J.EJMECH.2018.05.024

Abstract: Fucosylated chondroitin sulfate (FCS), an unusual glycosaminoglycan with fucose side chains, is a promising anticoagulant agent. To assess the effect of its structure on anticoagulant activity, its derivatives with various degrees of fucosylation (DF), molecular weights (Mw) and sulfation patterns were prepared and characterized. Biological tests showed that their APTT (activated partial thromboplastin time) prolonging activity and intrinsic factor Xase complex (factor IXa-VIIIa-Ca

Structural Elucidation and Biological Activity of a Highly Regular Fucosylated Glycosaminoglycan from the Edible Sea Cucumber Stichopus herrmanni

Publisher: American Chemical Society (ACS)

Date: 17-10-2017

DOI: 10.1021/ACS.JAFC.7B03867

Abstract: Edible sea cucumbers are widely used as a health food and medicine. A fucosylated glycosaminoglycan (FG) was purified from the high-value sea cucumber Stichopus herrmanni. Its physicochemical properties and structure were analyzed and characterized by chemical and instrumental methods. Chemical analysis indicated that this FG with a molecular weight of ∼64 kDa is composed of N-acetyl-d-galactosamine, d-glucuronic acid (GlcA), and l-fucose. Structural analysis clarified that the FG contains the chondroitin sulfate E-like backbone, with mostly 2,4-di-O-sulfated (85%) and some 3,4-di-O-sulfated (10%) and 4-O-sulfated (5%) fucose side chains that link to the C3 position of GlcA. This FG is structurally highly regular and homogeneous, differing from the FGs of other sea cucumbers, for its sulfation patterns are simpler. Biological activity assays indicated that it is a strong anticoagulant, inhibiting thrombin and intrinsic factor Xase. Our results expand the knowledge on structural types of FG and illustrate its biological activity as a functional food material.

Kunming Institute Of Botany Chinese Academy Of Sciences

Location: China

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Tianjin University

Location: China

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Kunming Institute Of Botany, Chinese Academy Of Sciences

Location: No location found

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