Enzymatic synthesis of chondroitin sulfate E to attenuate bacterial lipopolysaccharide-induced organ damage
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Authors
Li, J.
Sparkenbaugh, E.
Su, G.
Zhang, F.
Xu, Y.
Xia, K.
He, P.
Baytas, S.
Pechauer, S.
Padmanabhan, A.
Issue Date
2020
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
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.
Description
ACS Central Science, 6, 1199−1207
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Enzymatic synthesis of chondroitin sulfate E to attenuate bacterial lipopolysaccharide-induced organ damage J. Li, E. Sparkenbaugh, G. Su, F. Zhang, Y. Xu, K. Xia, P. He, S. Baytas, S. Pechauer, A. Padmanabhan, R. J. Linhardt, R. Pawlinski, J. Liu, ACS Central Science, 6, 1199−1207, 2020.
Publisher
American Chemical Society (ACS)