Enzymatic synthesis of chondroitin sulfate E to attenuate bacterial lipopolysaccharide-induced organ damage

Li, J.
Sparkenbaugh, E.
Su, G.
Zhang, F.
Xu, Y.
Xia, K.
He, P.
Baytas, S.
Pechauer, S.
Padmanabhan, A.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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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.
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.
ACS Central Science, 6, 1199−1207
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
American Chemical Society (ACS)
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
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