Guangli Yu

Chemical Structures and Bioactivities of Sulfated Polysaccharides from Marine Algae

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.

Structural studies on κ-carrageenan derived oligosaccharides

Oligosaccharides were prepared through mild hydrochloric acid hydrolysis of -carrageenan from Kappaphycus striatum carrageenan. Three oligosaccharides were purified by strong-anion exchange high-performance chromatography. Their structure was elucidated using mass spectral and NMR data. Negative-ion electrospray ionization (ESI) mass spectra at different fragmentor voltages provided the molecular weight of the compounds and unraveled the fragmentation pattern of the -carrageenan oligosaccharides. 2D NMR techniques, including 1 H– 1 H COSY, 1 H– 1 H TOCSY and 13 C– 1 H HMQC, were performed to determine the structure of a trisulfated pentasaccharide. 1D NMR and ESIMS were used to determine the structures of a -carrageenan-derived pentasaccharide, heptasaccharide, and an undecasaccharide. All the oligosaccharides characterized have a 4-O-sulfo-D-galactopyranose residue at both the reducing and nonreducing ends.

Sequence determination and anticoagulant and antithrombotic activities of a novel sulfated fucan isolated from the sea cucumber Isostichopus badionotus.

BACKGROUND The aim is to analyze the structure, anticoagulant and antithrombotic activities of a sulfated fucan isolated from sea cucumber Isostichopus badionotus (fucan-Ib). METHODS Fucan-Ib was hydrolyzed under mild acid conditions. The oligosaccharide fragments were fractionated by gel-filtration chromatography and the structures were determined by negative-ion electrospray tandem mass spectrometry with collision-induced dissociation and two-dimensional NMR. Anticoagulant activities were measured by activated partial thromboplastin, thrombin and prothrombin times, and by in vitro inhibition experiments with factors IIa and Xa. Antithrombotic activities were determined in vitro by measuring the length and weight of the thrombus generated. RESULT The linear polysaccharide sequence of fucan-Ib was deduced from the structures of its oligosaccharide fragments produced by acid hydrolysis. Under mild conditions, the glycosidic bonds between the non-sulfated and 2,4-O-disulfated fucose residues were selectively cleaved and highly ordered oligosaccharide fragments with a tetrasaccharide repeating unit [→3Fuc(2S,4S)α1→3Fuc(2S)α1→3Fuc(2S)α1→3Fucα1→]n were obtained. In in vitro assays fucan-Ib showed good anticoagulant and antithrombotic activities compared with heparin and the fucosylated chondroitin sulfate isolated from the same source (fCS-Ib). The two polysaccharides, fucan-Ib and fCS-Ib, differ in the mechanism of action; the former exhibited activity mainly by potentiation of antithrombin acted on thrombin and factor Xa whereas the latter mainly through heparin cofactor II. CONCLUSION Fucan-Ib has a well defined structure with tetrasaccharide tandem repeats and good anticoagulant and antithrombotic activities. GENERAL IMPORTANCE: Fucan-Ib has a well defined structure and can be readily quality-controlled, and therefore has potential therapeutic value as an affective antithrombotic drug with low risk of bleeding.

Sequence analysis of alginate-derived oligosaccharides by negative-ion electrospray tandem mass spectrometry.

Negative-ion electrospray tandem mass spectrometry (ES-MS/MS) with collision-induced dissociation (CID) is attempted for sequence determination of alginate oligosaccharides, derived from polyanionic alginic acid, polymannuronate, and polyguluronate by partial depolymerization using either alginate lyase or mild acid hydrolysis. Sixteen homo- and hetero-oligomeric fragments were obtained after fractionation by gel-filtration and strong anion exchange high performance liquid chromatography. The product-ion spectra of these alginate oligosaccharides were dominated by intense B-, C-, Y-, and Z-type ions together with 0,2A- and 2,5A-ions of lower intensities. Internal mannuronate residues (M) produce weak but specific decarboxylated Zint-ions (Zint − 44 Da; int: denotes internal), which can be used for distinction of M and a guluronate residue (G) at an internal position. A reducing terminal M or G, although neither gives rise to a specific ion, can be identified by differences in the intensity ratio of fragment ions of the reducing terminal residue [2,5Ared]/[0,4Ared] (red: denotes reducing terminal).

Adsorption of heavy metal ions, dyes and proteins by chitosan composites and derivatives — A review

Chitosan composites and derivatives have gained wide attentions as effective biosorbents due to their low costs and high contents of amino and hydroxyl functional groups. They have showed significant potentials of removing metal ions, dyes and proteins from various media. Chemical modifications that lead to the formation of the chitosan derivatives and chitosan composites have been extensively studied and widely reported in literatures. The aims of this review were to summarize the important information of the bioactivities of chitosan, highlight the various preparation methods of chitosan-based active biosorbents, and outline its potential applications in the adsorption of heavy metal ions, dyes and proteins from wastewater and aqueous solutions.

Moisture absorption and retention properties, and activity in alleviating skin photodamage of collagen polypeptide from marine fish skin

Collagen polypeptides were prepared from cod skin. Moisture absorption and retention properties of collagen polypeptides were determined at different relative humidities. In addition, the protective effects of collagen polypeptide against UV-induced damage to mouse skin were evaluated. Collagen polypeptides had good moisture absorption and retention properties and could alleviate the damage induced by UV radiation. The action mechanisms of collagen polypeptide mainly involved enhancing immunity, reducing the loss of moisture and lipid, promoting anti-oxidative properties, inhibiting the increase of glycosaminoglycans, repairing the endogenous collagen and elastin protein fibres, and maintaining the ratio of type III to type I collagen.

Purification and identification of immunomodulating peptides from enzymatic hydrolysates of Alaska pollock frame

To prepare immunomodulating peptides from Alaska pollock frame (APF) hydrolysates, trypsin was employed for enzymatic hydrolysis, and the immunomodulating activities of the hydrolysates were studied using splenic lymphocytes proliferation assay. The highest activity of the hydrolysates was reached when DH ranged from 15% to 18%. The peptide fractions which exhibited the highest activity were further purified using ion exchange chromatography, gel filtration chromatography, and RP-HPLC. The peptides were identified using nano-LC-ESI mass spectrometry. Finally, three immunomodulating peptides were obtained, and the amino acid sequences were Asn-Gly-Met-Thr-Tyr, Asn-Gly-Leu-Ala-Pro, and Trp-Thr, respectively. The lymphocyte proliferation rates were 35.92%, 32.96%, and 31.35% in the presence of 20 μg/ml purified peptides, respectively. Therefore, the results demonstrated that the APF proteins hydrolysates prepared by trypsin could serve as a source of peptides with immunomodulating activity. It provided a scientific basis for the preparation of immunomodulating peptides.

Elevate Level of Glycosaminoglycans and Altered Sulfation Pattern of Chondroitin Sulfate Are Associated with Differentiation Status and Histological Type of Human Primary Hepatic Carcinoma

Objectives: The characteristics of glycosaminoglycans (GAGs) in many carcinomas have been reported to be different from those in normal tissues, which can be used as prognostic indices in some cancers. However, the difference in GAG characteristics among various differentiation status or histological types of the same cancer has not been described. The aim of this study was to investigate the relationship between GAG characteristics and human primary hepatic carcinomas of divers differentiation status or histological type. Methods: GAGs from intrahepatic cholangiocarcinomas and differently differentiated hepatocellular carcinomas were extracted, purified and enzymatically digested. Their content, relative molecular size distribution and disaccharide composition were analyzed and compared using electrophoresis and high-performance liquid chromatography. Results: A progressive increase in the content of chondroitin sulfate, low molecular size GAGs, and nonsulfated and disulfated chondroitin sulfate disaccharide units, together with a gradual decrease in heparan sulfate, have been found as the differentiation status of hepatocellular carcinoma became poorer. A significant increase in hyaluronic acid, which only slightly increased in hepatocellular carcinoma, was found in intrahepatic cholangiocarcinomas. Conclusion: The alterations in GAG characteristics in primary hepatic carcinoma were associated with both the differentiation status and the histological type of the tumor.

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

A fucoidan from the brown alga Hizikia fusiforme was extracted with hot water and fractionated by anion-exchange chromatography. The main fraction YF5 was depolymerized by partial acid hydrolysis and further purified by gel filtration chromatograph. The sequences of oligosaccharides generated were then determined by ES-CID-MS/MS, which gave directly information on the structural heterogeneity of fucoidan from H. fusiforme. It was shown that YF5 had a backbone of a repeating disaccharide unit of [→4GlcAβ1,2Manα1→], in good agreement with previous report by NMR and methylation analysis. In the product-ion spectra, the unique (0.2)A type fragmentation was important to establish the presence of a 2-linked Man in the backbone structure. In addition, abundant novel heterogeneous branched structural fragments were also detected and characterized: Fuc1,3Fuc, Fuc1,3Gal, Fuc1,4GlcA, Gal1,4Gal, Gal1,4GlcA and GlcA1,4GlcA. The sulfation mainly occurred at C2 or C4 of the fucose residue and C2, C4 or C6 of the galactose residue.

Effect and Limitation of Excess Ammonium on the Release of O-Glycans in Reducing Forms from Glycoproteins under Mild Alkaline Conditions for Glycomic and Functional Analysis

Ammonium-based alkali-catalyzed β-elimination under nonreducing conditions was investigated in detail for the stability of the released mucin-type O-glycan chains with β1,3-linked cores. In contrast to the previously studied β1,4-linkage of the N-glycan-type, which was shown to be stable under the ammonium-based alkaline conditions, the β1,3-linkage is labile toward alkaline treatment and considerable peeling was observed with both model heptasaccharides and standard glycoproteins. The former include eight reducing glucoheptasaccharides with different and commonly occurring linkages (α1,2-, β1,2-, α1,3-, β1,3-, α1,4-, β1,4-, α1,6-, and β1,6-linkages), and the latter include mucin-type bovine submaxillary mucin and bovine fetuin, which contains both O- and N-glycans. The results indicated that complete prevention of peeling under nonreducing alkali-catalyzed hydrolysis conditions remains difficult. The yields of released O- and N-glycans were also assessed by use of the two glycoproteins as models. Compared with conventional procedures, Carlson degradation for O-glycan release and PNGase F digestion for N-glycan release, the nonreducing ammonium-based alkaline hydrolysis gave lower yields. Great care has to be taken when employing such nonreducing alkaline conditions in glycomic analysis and in obtaining glycoprotein glycans for functional studies.