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Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate Bacteria Lipopolysaccharide-Induced Organ Damage
[Image: see text] Chondroitin sulfate E (CS-E) is a sulfated polysaccharide that contains repeating disaccharides of 4,6-disulfated N-acetylgalactosamine and glucuronic acid residues. Here, we report the enzymatic synthesis of three homogeneous CS-E oligosaccharides, including CS-E heptasaccharide (...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379384/ https://www.ncbi.nlm.nih.gov/pubmed/32724854 http://dx.doi.org/10.1021/acscentsci.0c00712 |
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author | Li, Jine Sparkenbaugh, Erica M. Su, Guowei Zhang, Fuming Xu, Yongmei Xia, Ke He, Pen Baytas, Sultan Pechauer, Shannon Padmanabhan, Anand Linhardt, Robert J. Pawlinski, Rafal Liu, Jian |
author_facet | Li, Jine Sparkenbaugh, Erica M. Su, Guowei Zhang, Fuming Xu, Yongmei Xia, Ke He, Pen Baytas, Sultan Pechauer, Shannon Padmanabhan, Anand Linhardt, Robert J. Pawlinski, Rafal Liu, Jian |
author_sort | Li, Jine |
collection | PubMed |
description | [Image: see text] Chondroitin sulfate E (CS-E) is a sulfated polysaccharide that contains repeating disaccharides of 4,6-disulfated N-acetylgalactosamine and glucuronic acid residues. Here, we report the enzymatic synthesis of three homogeneous CS-E oligosaccharides, including CS-E heptasaccharide (CS-E 7-mer), CS-E tridecasaccharide (CS-E13-mer), and CS-E nonadecasaccharide (CS-E 19-mer). The anti-inflammatory effect of CS-E 19-mer was investigated in this study. CS-E 19-mer neutralizes the cytotoxic effect of histones in a cell-based assay and in mice. We also demonstrate that CS-E 19-mer treatment improves survival and protects against organ damage in a mouse model of endotoxemia induced by bacterial lipopolysaccharide (LPS). CS-E19-mer directly interacts with circulating histones in the plasma from LPS-challenged mice. CS-E 19-mer does not display anticoagulant activity nor react with heparin-induced thrombocytopenia antibodies isolated from patients. The successful synthesis of CS-E oligosaccharides provides structurally defined carbohydrates for advancing CS-E research and offers a potential therapeutic agent to treat life-threatening systemic inflammation. |
format | Online Article Text |
id | pubmed-7379384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-73793842020-07-27 Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate Bacteria Lipopolysaccharide-Induced Organ Damage Li, Jine Sparkenbaugh, Erica M. Su, Guowei Zhang, Fuming Xu, Yongmei Xia, Ke He, Pen Baytas, Sultan Pechauer, Shannon Padmanabhan, Anand Linhardt, Robert J. Pawlinski, Rafal Liu, Jian ACS Cent Sci [Image: see text] Chondroitin sulfate E (CS-E) is a sulfated polysaccharide that contains repeating disaccharides of 4,6-disulfated N-acetylgalactosamine and glucuronic acid residues. Here, we report the enzymatic synthesis of three homogeneous CS-E oligosaccharides, including CS-E heptasaccharide (CS-E 7-mer), CS-E tridecasaccharide (CS-E13-mer), and CS-E nonadecasaccharide (CS-E 19-mer). The anti-inflammatory effect of CS-E 19-mer was investigated in this study. CS-E 19-mer neutralizes the cytotoxic effect of histones in a cell-based assay and in mice. We also demonstrate that CS-E 19-mer treatment improves survival and protects against organ damage in a mouse model of endotoxemia induced by bacterial lipopolysaccharide (LPS). CS-E19-mer directly interacts with circulating histones in the plasma from LPS-challenged mice. CS-E 19-mer does not display anticoagulant activity nor react with heparin-induced thrombocytopenia antibodies isolated from patients. The successful synthesis of CS-E oligosaccharides provides structurally defined carbohydrates for advancing CS-E research and offers a potential therapeutic agent to treat life-threatening systemic inflammation. American Chemical Society 2020-07-01 2020-07-22 /pmc/articles/PMC7379384/ /pubmed/32724854 http://dx.doi.org/10.1021/acscentsci.0c00712 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Li, Jine Sparkenbaugh, Erica M. Su, Guowei Zhang, Fuming Xu, Yongmei Xia, Ke He, Pen Baytas, Sultan Pechauer, Shannon Padmanabhan, Anand Linhardt, Robert J. Pawlinski, Rafal Liu, Jian Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate Bacteria Lipopolysaccharide-Induced Organ Damage |
title | Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate
Bacteria Lipopolysaccharide-Induced Organ Damage |
title_full | Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate
Bacteria Lipopolysaccharide-Induced Organ Damage |
title_fullStr | Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate
Bacteria Lipopolysaccharide-Induced Organ Damage |
title_full_unstemmed | Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate
Bacteria Lipopolysaccharide-Induced Organ Damage |
title_short | Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate
Bacteria Lipopolysaccharide-Induced Organ Damage |
title_sort | enzymatic synthesis of chondroitin sulfate e to attenuate
bacteria lipopolysaccharide-induced organ damage |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379384/ https://www.ncbi.nlm.nih.gov/pubmed/32724854 http://dx.doi.org/10.1021/acscentsci.0c00712 |
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