Sulfated polysaccharides and their lower molecular weight oligosaccharide derivatives from marine macroalgae have been shown to possess a variety of biological activities. The present paper will review the recent progress in research on the structural chemistry and the bioactivities of these marine algal biomaterials. In particular, it will provide an update on the structural chemistry of the major sulfated polysaccharides synthesized by seaweeds including the galactans (e.g., agarans and carrageenans), ulvans, and fucans. It will then review the recent findings on the anticoagulant/antithrombotic, antiviral, immuno-inflammatory, antilipidemic and antioxidant activities of sulfated polysaccharides and their potential for therapeutic application.

Chemical Structures and Bioactivities of Sulfated Polysaccharides from Marine Algae

https://researchrepository.ucd.ie/bitstream/10197/8191/1/Garcia-Vaquero_et_al_2016._Polysaccharides.pdf

Polysaccharides from macroalgae: Recent advances, innovative technologies and challenges in extraction and purification

E-selectin is the inducible adhesion protein on the surface of endothelial cells which has a crucial role in the initial stages of recruitment of leucocytes to sites of inflammation. In addition, it is almost certainly involved in tumor cell adhesion and metastasis. This report is concerned with identification of a new class of oligosaccharide ligand--sulfate-containing--for the human E-selectin molecule from among oligosaccharides on an ovarian cystadenoma glycoprotein. This has been achieved by application of the neoglycolipid technology to oligosaccharides released from the glycoprotein by mild alkaline beta-elimination. Oligosaccharides were conjugated to lipid, resolved by thin-layer chromatography, and tested for binding by Chinese hamster ovary cells which had been transfected to express the full-length E-selectin molecule. Several components with strong E-selectin binding activity were revealed among acidic oligosaccharides. The smallest among these was identified by liquid secondary ion mass spectrometric analysis of the neoglycolipid, in conjunction with methylation analysis of the purified oligosaccharide preparation as an equimolar mixture of the Le(a)- and Le(x)/SSEA-1-type fucotetrasaccharides sulfated at position 3 of outer galactose: [formula: see text] To our knowledge this is the first report of a sulfofucooligosaccharide ligand for E-selectin. The binding activity is substantially greater than those of lipid-linked Le(a) and Le(x)/SSEA-1 sequences and is at least equal to that of the 3'-sialyl-Le(x)/SSEA-1 glycolipid analogue.

Novel sulfated ligands for the cell adhesion molecule E-selectin rreveled by the neoglycolipid technology among O-liked oligo-saccharides on an ovarin cystadenoma glycoprotein

Fucoidan is a polysaccharide largely made up of l-fucose and sulfate groups. Fucoidan is favorable worldwide, especially amongst the food and pharmaceutical industry as a consequence of its promising therapeutic effects. Its applaudable biological functions are ascribed to its unique biological structure. Classical bioactivities associated with fucoidan include anti-oxidant, anti-tumor, anti-coagulant, anti-thrombotic, immunoregulatory, anti-viral and anti-inflammatory effects. More recently, a variety of in vitro and in vivo studies have been carried out to further highlight its therapeutic potentials. This review focuses on the progress towards understanding fucoidan and its biological activities, which may be beneficial as a future therapy. Hence, we have summarized in vitro and in vivo studies that were done within the current decade. We expect this review and a variety of others can contribute as a theoretical basis for understanding and inspire further product development of fucoidan.

https://www.mdpi.com/1660-3397/17/9/487/pdf

Therapeutic Effects of Fucoidan: A Review on Recent Studies

The antiviral activity of polysaccharides and their derivatives.

Development of novel anti-influenza A virus (IAV) drugs with high efficiency and low toxicity is critical for preparedness against influenza outbreaks. Herein, we investigated the anti-IAV activities and mechanisms of fucoidan in vitro and in vivo. The results showed that a fucoidan KW derived from brown algae Kjellmaniella crassifolia effectively blocked IAV infection in vitro with low toxicity. KW possessed broad anti-IAV spectrum and low tendency of induction of viral resistance, superior to the anti-IAV drug amantadine. KW was capable of inactivating virus particles before infection and blocked some stages after adsorption. KW could bind to viral neuraminidase (NA) and inhibit the activity of NA to block the release of IAV. KW also interfered with the activation of EGFR, PKCα, NF-κB, and Akt, and inhibited both IAV endocytosis and EGFR internalization in IAV-infected cells, suggesting that KW may also inhibit cellular EGFR pathway. Moreover, intranasal administration of KW markedly improved survival and decreased viral titers in IAV-infected mice. Therefore, fucoidan KW has the potential to be developed into a novel nasal drop or spray for prevention and treatment of influenza in the future.

/pdf/inhibition-of-influenza-a-virus-infection-by-fucoidan-i00y9tbkm7.pdf

Inhibition of Influenza A Virus Infection by Fucoidan Targeting Viral Neuraminidase and Cellular EGFR Pathway

Glycosaminoglycans (GAGs) play vital roles in many biological processes and are naturally present as complex mixtures of polysaccharides with tremendous structural heterogeneity, including many structural isomers. Mass spectrometric analysis of GAG isomers, in particular highly sulfated heparin (Hep) and heparan sulfate (HS), is challenging because of their structural similarity and facile sulfo losses during analysis. Herein, we show that highly sulfated Hep/HS isomers may be resolved by gated-trapped ion mobility spectrometry (gated-TIMS) with negligible sulfo losses. Subsequent negative electron transfer dissociation (NETD) tandem mass spectrometry (MS/MS) analysis of TIMS-separated Hep/HS isomers generated extensive glycosidic and cross-ring fragments for confident isomer differentiation and structure elucidation. The high mobility resolution and preservation of labile sulfo modifications afforded by gated-TIMS MS analysis also allowed relative quantification of highly sulfated heparin isomers. These results show that the gated-TIMS-NETD MS/MS approach is useful for both qualitative and quantitative analysis of highly sulfated Hep/HS compounds in a manner not possible with other techniques.

Characterization and Quantification of Highly Sulfated Glycosaminoglycan Isomers by Gated-Trapped Ion Mobility Spectrometry Negative Electron Transfer Dissociation MS/MS

Analysis of structural heterogeneity of fucoidan from Hizikia fusiforme by ES-CID-MS/MS.

Three kinds of polysaccharides: GFW, GFH and GFA, were sequentially extracted from a red alga Gloiopeltis furcata with 25°C and 85°C water, and 60 4% NaOH water solution. Based on the defatted alga, the yields of the polysaccharide were 57.9%, 2.5% and 2.6%, respectively. Their monosaccharide compositions, average molecular weights and structural characters were determined by gas chromatography (GC), high performance liquid chromatography (HPLC), fourier transform infrared spectroscopy (FTIR) or 13C-NMR spectroscopy. The results showed that GFW, GFH and GFA were all composed of D-galactose (Gal) and 3,6-anhydro-L-galactose (AnG), and particularly GFA also contained xylose (Xyl). The average molecular weights of GFW, GFH and GFA were 22.6 kD, 26.5 kD and 49.8 kD, respectively, with the respective sulfate content 31.2%, 25.1% and 22.7%. The data of FTIR and 13C-NMR confirmed the sulfate ester location at C6 of galactose. It is concluded that all the three polysaccharides extracted from Gloiopeltis furcata were sulfated galactans, two being sulfated-agarose, and one being xylose-containing sulfated galactan.

Extraction, isolation and structural characterization of polysaccharides from a red alga Gloiopeltis furcata

Humans express seven heparan sulfate (HS) 3-O-sulfotransferases that differ in substrate specificity and tissue expression. Although genetic studies have indicated that 3-O-sulfated HS modulates many biological processes, ligand requirements for proteins engaging with HS modified by 3-O-sulfate (3-OS) have been difficult to determine. In particular, the context in which the 3-OS group needs to be presented for binding is largely unknown. We describe herein a modular synthetic approach that can provide structurally diverse HS oligosaccharides with and without 3-OS. The methodology was employed to prepare 27 hexasaccharides that were printed as a glycan microarray to examine ligand requirements of a wide range of HS-binding proteins. The binding selectivity of antithrombin-III (AT-III) compared well with anti-Factor Xa activity supporting robustness of the array technology. Many of the other examined HS-binding proteins required an IdoA2S-GlcNS3S6S sequon for binding but exhibited variable dependence for the 2-OS and 6-OS moieties, and a GlcA or IdoA2S residue neighboring the central GlcNS3S. The HS oligosaccharides were also examined as inhibitors of cell entry by herpes simplex virus type 1, which, surprisingly, showed a lack of dependence of 3-OS, indicating that, instead of glycoprotein D (gD), they competitively bind to gB and gC. The compounds were also used to examine substrate specificities of heparin lyases, which are enzymes used for depolymerization of HS/heparin for sequence determination and production of therapeutic heparins. It was found that cleavage by lyase II is influenced by 3-OS, while digestion by lyase I is only affected by 2-OS. Lyase III exhibited sensitivity to both 3-OS and 2-OS.

https://www.pnas.org/content/pnas/118/3/e2012935118.full.pdf

Jiandong Wu

Papers

Inhibition of Influenza A Virus Infection by Fucoidan Targeting Viral Neuraminidase and Cellular EGFR Pathway

Characterization and Quantification of Highly Sulfated Glycosaminoglycan Isomers by Gated-Trapped Ion Mobility Spectrometry Negative Electron Transfer Dissociation MS/MS

Analysis of structural heterogeneity of fucoidan from Hizikia fusiforme by ES-CID-MS/MS.

Extraction, isolation and structural characterization of polysaccharides from a red alga Gloiopeltis furcata

The 3-O-sulfation of heparan sulfate modulates protein binding and lyase degradation