The Experts below are selected from a list of 18 Experts worldwide ranked by ideXlab platform
Clive P. Page - One of the best experts on this subject based on the ideXlab platform.
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Fucosylated Chondroitin Sulfates from the Body Wall of the Sea Cucumber Holothuria forskali CONFORMATION, SELECTIN BINDING, AND BIOLOGICAL ACTIVITY
The Journal of biological chemistry, 2014Co-Authors: Charalampos G. Panagos, Derek Thomson, Claire Moss, Adam D. Hughes, Maeve Kelly, Yan Liu, Wengang Chai, Radhakrishnan Venkatasamy, Domenico Spina, Clive P. PageAbstract:Fucosylated chondroitin sulfate (fCS) extracted from the sea cucumber Holothuria forskali is composed of the following repeating trisaccharide unit: →3)GalNAcβ4,6S(1→4) [FucαX(1→3)]GlcAβ(1→, where X stands for different sulfation patterns of fucose (X = 3,4S (46%), 2,4S (39%), and 4S (15%)). As revealed by NMR and molecular dynamics simulations, the fCS repeating unit adopts a conformation similar to that of the Lex blood group determinant, bringing several sulfate groups into close proximity and creating large negative patches distributed along the helical skeleton of the CS backbone. This may explain the high affinity of fCS oligosaccharides for L- and P-selectins as determined by microarray binding of fCS oligosaccharides prepared by Cu2+-catalyzed Fenton-type and Photochemical Depolymerization. No binding to E-selectin was observed. fCS poly- and oligosaccharides display low cytotoxicity in vitro, inhibit human neutrophil elastase activity, and inhibit the migration of neutrophils through an endothelial cell layer in vitro. Although the polysaccharide showed some anti-coagulant activity, small oligosaccharide fCS fragments had much reduced anticoagulant properties, with activity mainly via heparin cofactor II. The fCS polysaccharides showed prekallikrein activation comparable with dextran sulfate, whereas the fCS oligosaccharides caused almost no effect. The H. forskali fCS oligosaccharides were also tested in a mouse peritoneal inflammation model, where they caused a reduction in neutrophil infiltration. Overall, the data presented support the action of fCS as an inhibitor of selectin interactions, which play vital roles in inflammation and metastasis progression. Future studies of fCS-selectin interaction using fCS fragments or their mimetics may open new avenues for therapeutic intervention.
Robert J. Linhardt - One of the best experts on this subject based on the ideXlab platform.
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Controlled Photochemical Depolymerization of K5 Heparosan, a Bioengineered Heparin Precursor.
Carbohydrate polymers, 2011Co-Authors: Kyohei Higashi, Zhenyu Wang, Sayaka Masuko, Ujjwal Bhaskar, Eric Sterner, Fuming Zhang, Toshihiko Toida, Jonathan S. Dordick, Robert J. LinhardtAbstract:Abstract Heparosan is a polysaccharide, which serves as the critical precursor in heparin biosynthesis and chemoenzymatic synthesis of bioengineered heparin. Because the molecular weight of microbial heparosan is considerably larger than heparin, the controlled Depolymerization of microbial heparosan is necessary prior to its conversion to bioengineered heparin. We have previously reported that other acidic polysaccharides could be partially depolymerized with maintenance of their internal structure using a titanium dioxide-catalyzed Photochemical reaction. This photolytic process is characterized by the generation of reactive oxygen species that oxidize individual saccharide residues within the polysaccharide chain. Using a similar approach, a microbial heparosan from Escherichia coli K5 of molecular weight >15,000 was depolymerized to a heparosan of molecular weight 8000. The 1H NMR spectra obtained showed that the photolyzed heparosan maintained the same structure as the starting heparosan. The polysaccharide chains of the Photochemically depolymerized heparosan were also characterized by electrospray ionization-Fourier-transform mass spectrometry. While the chain of K5 heparosan starting material contained primarily an even number of saccharide residues, as a result of coliphage K5 lyase processing, both odd and even chain numbers were detected in the Photochemically depolymerized heparosan. These results suggest that the Photochemical Depolymerization of heparosan was a random process that can take place at either the glucuronic acid or the N-acetylglucosamine residue within the heparosan polysaccharide.
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Partial Depolymerization of pectin by a Photochemical reaction
Carbohydrate research, 2010Co-Authors: Jankana Burana-osot, Robert J. Linhardt, Noppamas Soonthornchareonnon, Saori Hosoyama, Toshihiko ToidaAbstract:Abstract Complex heterogeneous polysaccharides that comprise pectin were partially depolymerized by a Photochemical reaction using ultraviolet light in the presence of titanium dioxide catalyst. In a period of 6 h at pH 7, this UV/TiO2 process decreased the average molecular weight of pectin from 400 kDa to 200 kDa. The characterization of the partially depolymerized pectin, which was fractionated by size-exclusion chromatography, was performed by 1H NMR spectroscopy, and the spectra obtained showed that the resulting oligosaccharides and polysaccharides maintained the intact core structure of pectin. The monosaccharide content and Depolymerization profile were determined by high-performance anion-exchange chromatography coupled with pulsed amperometric detection. This controlled Photochemical Depolymerization technique might be useful for preparation of pectin oligosaccharides as an ingredient in food and pharmaceutical products.
Toshihiko Toida - One of the best experts on this subject based on the ideXlab platform.
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Controlled Photochemical Depolymerization of K5 Heparosan, a Bioengineered Heparin Precursor.
Carbohydrate polymers, 2011Co-Authors: Kyohei Higashi, Zhenyu Wang, Sayaka Masuko, Ujjwal Bhaskar, Eric Sterner, Fuming Zhang, Toshihiko Toida, Jonathan S. Dordick, Robert J. LinhardtAbstract:Abstract Heparosan is a polysaccharide, which serves as the critical precursor in heparin biosynthesis and chemoenzymatic synthesis of bioengineered heparin. Because the molecular weight of microbial heparosan is considerably larger than heparin, the controlled Depolymerization of microbial heparosan is necessary prior to its conversion to bioengineered heparin. We have previously reported that other acidic polysaccharides could be partially depolymerized with maintenance of their internal structure using a titanium dioxide-catalyzed Photochemical reaction. This photolytic process is characterized by the generation of reactive oxygen species that oxidize individual saccharide residues within the polysaccharide chain. Using a similar approach, a microbial heparosan from Escherichia coli K5 of molecular weight >15,000 was depolymerized to a heparosan of molecular weight 8000. The 1H NMR spectra obtained showed that the photolyzed heparosan maintained the same structure as the starting heparosan. The polysaccharide chains of the Photochemically depolymerized heparosan were also characterized by electrospray ionization-Fourier-transform mass spectrometry. While the chain of K5 heparosan starting material contained primarily an even number of saccharide residues, as a result of coliphage K5 lyase processing, both odd and even chain numbers were detected in the Photochemically depolymerized heparosan. These results suggest that the Photochemical Depolymerization of heparosan was a random process that can take place at either the glucuronic acid or the N-acetylglucosamine residue within the heparosan polysaccharide.
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Partial Depolymerization of pectin by a Photochemical reaction
Carbohydrate research, 2010Co-Authors: Jankana Burana-osot, Robert J. Linhardt, Noppamas Soonthornchareonnon, Saori Hosoyama, Toshihiko ToidaAbstract:Abstract Complex heterogeneous polysaccharides that comprise pectin were partially depolymerized by a Photochemical reaction using ultraviolet light in the presence of titanium dioxide catalyst. In a period of 6 h at pH 7, this UV/TiO2 process decreased the average molecular weight of pectin from 400 kDa to 200 kDa. The characterization of the partially depolymerized pectin, which was fractionated by size-exclusion chromatography, was performed by 1H NMR spectroscopy, and the spectra obtained showed that the resulting oligosaccharides and polysaccharides maintained the intact core structure of pectin. The monosaccharide content and Depolymerization profile were determined by high-performance anion-exchange chromatography coupled with pulsed amperometric detection. This controlled Photochemical Depolymerization technique might be useful for preparation of pectin oligosaccharides as an ingredient in food and pharmaceutical products.
Charalampos G. Panagos - One of the best experts on this subject based on the ideXlab platform.
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Fucosylated Chondroitin Sulfates from the Body Wall of the Sea Cucumber Holothuria forskali CONFORMATION, SELECTIN BINDING, AND BIOLOGICAL ACTIVITY
The Journal of biological chemistry, 2014Co-Authors: Charalampos G. Panagos, Derek Thomson, Claire Moss, Adam D. Hughes, Maeve Kelly, Yan Liu, Wengang Chai, Radhakrishnan Venkatasamy, Domenico Spina, Clive P. PageAbstract:Fucosylated chondroitin sulfate (fCS) extracted from the sea cucumber Holothuria forskali is composed of the following repeating trisaccharide unit: →3)GalNAcβ4,6S(1→4) [FucαX(1→3)]GlcAβ(1→, where X stands for different sulfation patterns of fucose (X = 3,4S (46%), 2,4S (39%), and 4S (15%)). As revealed by NMR and molecular dynamics simulations, the fCS repeating unit adopts a conformation similar to that of the Lex blood group determinant, bringing several sulfate groups into close proximity and creating large negative patches distributed along the helical skeleton of the CS backbone. This may explain the high affinity of fCS oligosaccharides for L- and P-selectins as determined by microarray binding of fCS oligosaccharides prepared by Cu2+-catalyzed Fenton-type and Photochemical Depolymerization. No binding to E-selectin was observed. fCS poly- and oligosaccharides display low cytotoxicity in vitro, inhibit human neutrophil elastase activity, and inhibit the migration of neutrophils through an endothelial cell layer in vitro. Although the polysaccharide showed some anti-coagulant activity, small oligosaccharide fCS fragments had much reduced anticoagulant properties, with activity mainly via heparin cofactor II. The fCS polysaccharides showed prekallikrein activation comparable with dextran sulfate, whereas the fCS oligosaccharides caused almost no effect. The H. forskali fCS oligosaccharides were also tested in a mouse peritoneal inflammation model, where they caused a reduction in neutrophil infiltration. Overall, the data presented support the action of fCS as an inhibitor of selectin interactions, which play vital roles in inflammation and metastasis progression. Future studies of fCS-selectin interaction using fCS fragments or their mimetics may open new avenues for therapeutic intervention.
Derek Thomson - One of the best experts on this subject based on the ideXlab platform.
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Fucosylated Chondroitin Sulfates from the Body Wall of the Sea Cucumber Holothuria forskali CONFORMATION, SELECTIN BINDING, AND BIOLOGICAL ACTIVITY
The Journal of biological chemistry, 2014Co-Authors: Charalampos G. Panagos, Derek Thomson, Claire Moss, Adam D. Hughes, Maeve Kelly, Yan Liu, Wengang Chai, Radhakrishnan Venkatasamy, Domenico Spina, Clive P. PageAbstract:Fucosylated chondroitin sulfate (fCS) extracted from the sea cucumber Holothuria forskali is composed of the following repeating trisaccharide unit: →3)GalNAcβ4,6S(1→4) [FucαX(1→3)]GlcAβ(1→, where X stands for different sulfation patterns of fucose (X = 3,4S (46%), 2,4S (39%), and 4S (15%)). As revealed by NMR and molecular dynamics simulations, the fCS repeating unit adopts a conformation similar to that of the Lex blood group determinant, bringing several sulfate groups into close proximity and creating large negative patches distributed along the helical skeleton of the CS backbone. This may explain the high affinity of fCS oligosaccharides for L- and P-selectins as determined by microarray binding of fCS oligosaccharides prepared by Cu2+-catalyzed Fenton-type and Photochemical Depolymerization. No binding to E-selectin was observed. fCS poly- and oligosaccharides display low cytotoxicity in vitro, inhibit human neutrophil elastase activity, and inhibit the migration of neutrophils through an endothelial cell layer in vitro. Although the polysaccharide showed some anti-coagulant activity, small oligosaccharide fCS fragments had much reduced anticoagulant properties, with activity mainly via heparin cofactor II. The fCS polysaccharides showed prekallikrein activation comparable with dextran sulfate, whereas the fCS oligosaccharides caused almost no effect. The H. forskali fCS oligosaccharides were also tested in a mouse peritoneal inflammation model, where they caused a reduction in neutrophil infiltration. Overall, the data presented support the action of fCS as an inhibitor of selectin interactions, which play vital roles in inflammation and metastasis progression. Future studies of fCS-selectin interaction using fCS fragments or their mimetics may open new avenues for therapeutic intervention.