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Fucoidans are natural sulfated polysaccharides that have a wide range of biological functions and are regarded as promising antitumor agents. The activity of various fucoidans and their derivatives has been demonstrated in vitro on tumor cells of different histogenesis and in experiments on mice with grafted tumors. However, these experimental models showed low levels of antitumor activity and clinical trials did not prove that this class of compounds could serve as antitumor drugs. Nevertheless, the anti-inflammatory, antiangiogenic, immunostimulating, and anticoagulant properties of fucoidans, as well as their ability to stimulate hematopoiesis during cytostatic-based antitumor therapy, suggest that effective fucoidan-based drugs could be designed for the supportive care and symptomatic therapy of cancer patients. The use of fucoidans in cancer patients after chemotherapy and radiation therapy might promote the rapid improvement of hematopoiesis, while their anti-inflammatory, immunomodulatory, and anticoagulant effects have the potential to improve the quality of life of patients with advanced cancer. [ABSTRACT FROM AUTHOR]

A gene that encodes fucoidanase ffa2 in the marine bacterium Formosa algae strain KMM 3553T was cloned, and the protein (FFA2) was produced in Escherichia coli. Recombinant fucoidanase FFA2 was purified, and the biochemical properties of this enzyme were studied. The amino acid sequence of FFA2 showed 57% identity with known fucoidanase FcnA from Mariniflexile fucanivorans. The mass of the gene product FFA2 is 101.2 kDa (918 amino acid residues). Sequence analysis has revealed that fucoidanase FFA2 belongs to the GH107 (CAZy) family. Detailed substrate specificity was studied by using fucoidans from brown seaweeds as well as synthetic fucooligosaccharide with distinct structures. Fucoidanase FFA2 catalyzes the cleavage of (1→4)-α-glycosidic bonds in the fucoidan from Fucus evanescens within a structural fragment (→3)-α-L-Fucp2S-(1→4)-α-L-Fucp2S-(1→)n but not in a fragment (→3)-α-L-Fucp2S,4S-(1→4)-α-L-Fucp2S-(1→)n. Using synthetic di-, tetra- and octasaccharides built up of the alternative (1→4)- and (1→3)-linked α-L-Fucp2S units, the difference in substrate specificity and in the rate of enzymatic selectivity was investigated. Nonsulfated and persulfated synthetic oligosaccharides were not transformed by the enzyme. Therefore, FFA2 was specified as poly[(1→4)-α-L-fucoside-2-sulfate] glycanohydrolase. This enzyme could be used for the modification of natural fucoidans to obtain more regular and easier characterized derivatives useful for research and practical applications. [ABSTRACT FROM AUTHOR]

Sulfated polysaccharides of brown algae (fucoidans) attract great attention due to their high and strongly diversified biological activity. This review summarizes recent data on the structural variability of these polysaccharides and reports their anti- and proangiogenic properties. Recent publications have revealed that fucoidans isolated from different algal species may differ considerably in the structures of their backbones and branches, in both monosaccharide composition and sulfate content. It was found that the degree of sulfation significantly influences the biological properties of fucoidans. Additionally, fucoidan action in angiogenesis is highly dependent on molecular weight: antiangiogenic activity is connected with the high-molecular weight of polysaccharide molecules, whereas the low-molecular-weight fractions may act as proangiogenic agents. The influence of other fine structural details of fucoidans on angiogenesis remains to be established. [ABSTRACT FROM AUTHOR]

Anionic fucose-containing polysaccharides (fucoidans of brown seaweeds, sulfated fucans and fucosylated chondroitin sulfates of invertebrates) are attracting a rapidly growing research interest due to different types of their biological activity discovered in recent years. In particular, algal fucoidans are characterized by large structural variations depending on the species used for their isolation and by the lack of structural regularity due to random distribution of both carbohydrate and non-carbohydrate substituents along the polymer chains. These features make it difficult to find distinct correlations between structural elements and biological properties of polysaccharides. Nevertheless, there is expectation that systematic structural and biochemical studies of fucoidans will form a basis for the development of new drugs. Herewith we summarize our recent results on the influence of fucoidan structure on blood coagulation. [ABSTRACT FROM AUTHOR]

Three structurally different fucoidans from the brown seaweeds Saccharina latissima (SL), Fucus vesiculosus (FV), and Cladosiphon okamuranus (CO), two chemically modified fucoidans with a higher degree of sulfation (SL-S, CO-S), and a synthetic totally sulfated octasaccharide (OS), related to fucoidans, were assessed on anticoagulant and antithrombotic activities in different in vitro experiments. The effects were shown to depend on the structural features of the compounds tested. Native fucoidan SL with a degree of sulfation (DS) of 1.3 was found to be the most active sample, fucoidan FV (DS 0.9) demonstrated moderate activity, while the polysaccharide CO (DS 0.4) was inactive in all performed experiments, even at high concentrations. Additional introduction of sulfate groups into fucoidan SL slightly decreased the anticoagulant effect of SL-S, while sulfation of CO, giving rise to the preparation CO-S, increased the activity dramatically. The high level of anticoagulant activity of polysaccharides SL, SL-S, and CO-S was explained by their ability to form ternary complexes with ATIII-Xa and ATIII-IIa, as well as to bind directly to thrombin. Synthetic per-O-sulfated octasaccharide OS showed moderate anticoagulant effect, determined mainly by the interaction of OS with the factor Xa in the presence of ATIII. Comparable tendencies were observed in the antithrombotic properties of the compounds tested. [ABSTRACT FROM AUTHOR]

Abstract The brown alga Hormophysa cuneiformis collected from the coastal waters of Vietnam was used to isolate a mixture of sulfated polysaccharides FHC , which was fractionated further by anion-exchange chromatography on DEAE-Sephacel. The main fraction F3 eluted with 1.5 M NaCl contained essentially l -fucose, d -galactose and sulfate and has very complex NMR spectra. Desulfation to obtain F3deS followed by Smith degradation to obtain F3deS-Sm was used to simplify the structure of F3 , and all these preparations were characterized by methylation analysis and NMR spectra. A linear (1 → 3)-linked backbone built up of α- l -fucopyranose residues was identified as the main structural motif of molecules. Some fucose residues attached to position 4 of its 3-linked neighbor were found as branches. Galactose residues having both α- and β-configurations were found mostly at the periphery of molecules. They are present as (1 → 6)-linked disaccharide of two β- d -Gal p attached to position 4 of the backbone or as single α- d -Gal p attached to the same position. Sulfate groups in F3 may probably occupy any positions of the molecule. F3 acts as anticoagulant and is about half as active as the standard low-molecular mass heparin (enoxaparin). FHC was practically inactive in cytotoxicity test against six human cancer cell lines. Graphical abstract Image 1 Highlights • A fucoidan preparation was isolated from the brown alga Hormophysa cuneiformis. • Fractionation of fucoidan was carried out by anion-exchange chromatography. • Anticoagulant activity of fractions was shown to depend on degree of sulfation. • Polysaccharide structures were studied by chemical and spectral methods. • The presence of a sulfated branched galactofucan was detected. [ABSTRACT FROM AUTHOR]

Highlights: [•] Two sulfated fucoidan fractions F3 and F4 were isolated from S. polycystum. [•] The fractions have similar composition, but quite different chemical structures. [•] F4 has a sequence of 3-linked α-l-Fucp interspersed by 2-linked α-d-Galp residues. [•] The presence of 2-linked α-d-Galp should greatly modify the polymer conformation. [Copyright &y& Elsevier]

Abstract: The polysaccharide composition of a fucoidan preparation isolated from the brown alga Saccharina latissima (formerly Laminaria saccharina) was reinvestigated. The preparation was fractionated by anion-exchange chromatography, and the fractions obtained were analyzed by chemical methods combined with NMR spectroscopy. Several 2D procedures, including HSQC, HMQC-TOCSY, and HMQC-NOESY, were used to obtain reliable structural information from the complex spectra, and the signal assignments were additionally confirmed by comparison with the literature spectra of the related polysaccharides and synthetic oligosaccharides. In accordance with the previous data, the main polysaccharide component was shown to be a fucan sulfate containing a backbone of 3-linked α-l-fucopyranose residues sulfated at C-4 and/or at C-2 and branched at C-2 by single sulfated α-l-fucopyranose residues. In addition, three other types of sulfated polysaccharide molecules were detected in the total fucoidan preparation: (i) a fucogalactan having a backbone of 6-linked β-d-galactopyranose residues branched mainly at C-4 and containing both terminal galactose and fucose residues; (ii) a fucoglucuronomannan having a backbone of alternating 4-linked β-d-glucopyranosyluronic acid and 2-linked α-d-mannopyranose residues with α-l-fucopyranose residues as single branches at C-3 of α-d-Manp; and (iii) a fucoglucuronan having a backbone of 3-linked β-d-glucopyranosyluronic acid residues with α-l-fucopyranose residues as single branches at C-4. Hence, even a single algal species may contain, at least in minor amounts, several sulfated polysaccharides differing in molecular structure. Partial resolution of these polysaccharides has been accomplished, but unambiguous evidence on their presence as separate entities was not obtained. [ABSTRACT FROM AUTHOR]

Abstract: A fucoidan fraction composed of l-fucose, sulfate, and d-glucuronic acid in a molar proportion of about 1:1:0.25 and small amount of acetyl groups was isolated from the brown alga Chordaria flagelliformis. Several modified polysaccharides were prepared from the native fucoidan using solvolytic desulfation, carboxyl reduction, and partial acid hydrolysis. Polysaccharide structures were elucidated by methylation analysis and 1D and 2D NMR spectroscopy. The fucoidan was shown to contain a backbone of 3-linked α-l-fucopyranose residues, about one-third of which are glycosylated at C-2 by α-d-glucopyranosyluronic acid residues. About half of the latter residues are glycosylated at C-4 by single α-l-fucofuranose residues or by disaccharides α-l-Fucf-(1→2)-α-l-Fucf-(1→. Fucofuranose residues are mono- and disulfated at different positions, whereas some additional sulfate groups occupy C-2 and C-4 of the backbone, the latter position being also partially acetylated. [Copyright &y& Elsevier]

Abstract: A fucoidan consisting of l-fucose, sulfate and acetate in a molar proportion of 1:1:0.1 and small amounts of xylose and galactose were isolated from the brown seaweed Fucus serratus L. The fucoidan structure was investigated by 1D and 2D 1H and 13C NMR spectroscopy of its desulfated and de-O-acetylated derivatives as well as by methylation analysis of the native and desulfated polysaccharides. A branched structure was suggested for the fucoidan with a backbone of alternating 3- and 4-linked α-l-fucopyranose residues, →3)-α-l-Fucp-(1→4)-α-l-Fucp-(1→, about half of the 3-linked residues being substituted at C-4 by trifucoside units α-l-Fucp-(1→4)-α-l-Fucp-(1→3)-α-l-Fucp-(1→. Minor chains built up of 4-linked α-fucopyranose and β-xylose residues were also detected, but their location, as well as the position of galactose residues, remained unknown. Sulfate groups were shown to occupy mainly C-2 and sometimes C-4, although 3,4-diglycosylated and some terminal fucose residues may be nonsulfated. Acetate was found to occupy C-4 of 3-linked Fuc and C-3 of 4-linked Fuc in a ratio of about 7:3. [Copyright &y& Elsevier]

A fucoidan fraction consisting of l-fucose, sulfate, and acetate in a molar proportion of 1:1.21:0.08 was isolated from the brown seaweed Fucus distichus collected from the Barents Sea. The 13C NMR spectrum of the fraction was typical of regular polysaccharides containing disaccharide repeating units. According to 1D and 2D 1H and 13C NMR spectra, the fucoidan molecules are built up of alternating 3-linked α-l-fucopyranose 2,4-disulfate and 4-linked α-l-fucopyranose 2-sulfate residues: → 3)-α-l-Fucp-(2,4-di-SO3−)-(1 → 4)-α-l-Fucp-(2SO3−)-(1 →. The regular structure may be only slightly masked by random acetylation and undersulfation of several disaccharide repeating units. [Copyright &y& Elsevier]

A fucoidan consisting of l-fucose, sulfate and acetate in a molar proportion of 1:1.23:0.36 was isolated from the Pacific brown seaweed Fucus evanescens. The structures of its desulfated and de-O-acetylated derivatives were investigated by 1D and 2D 1H and 13C NMR spectroscopy, and the data obtained were confirmed by methylation analysis of the native and desulfated polysaccharides. The fucoidan was shown to contain a linear backbone of alternating 3- and 4-linked α-l-fucopyranose 2-sulfate residues: →3)-α-l-Fucp(2SO3−)-(1→4)-α-l-Fucp(2SO3−)-(1→. Additional sulfate occupies position 4 in a part of 3-linked fucose residues, whereas a part of the remaining hydroxyl groups is randomly acetylated. [Copyright &y& Elsevier]