当前位置: X-MOL 学术ACS Cent. Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate Bacteria Lipopolysaccharide-Induced Organ Damage.
ACS Central Science ( IF 12.7 ) Pub Date : 2020-07-01 , DOI: 10.1021/acscentsci.0c00712
Jine Li 1 , Erica M Sparkenbaugh 2 , Guowei Su 1 , Fuming Zhang 3 , Yongmei Xu 1 , Ke Xia 3 , Pen He 3 , Sultan Baytas 3 , Shannon Pechauer 4 , Anand Padmanabhan 5 , Robert J Linhardt 3 , Rafal Pawlinski 2 , Jian Liu 1
Affiliation  

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.

中文翻译:

酶促合成硫酸软骨素 E 以减轻细菌脂多糖诱导的器官损伤。

硫酸软骨素 E (CS-E) 是一种硫酸化多糖,含有 4,6-二硫酸化N-乙酰半乳糖胺和葡萄糖醛酸残基的重复二糖。在这里,我们报道了三种均相 CS-E 寡糖的酶促合成,包括 CS-E 七糖 ( CS-E 7-mer )、CS-E 十三糖 ( CS-E13-mer ) 和 CS -E 十九糖 ( CS-E 19-mer)。本研究研究了CS-E 19-mer的抗炎作用。CS-E 19-mer在基于细胞的测定和小鼠中中和组蛋白的细胞毒性作用。我们还证明了CS-E 19-mer在细菌脂多糖 (LPS) 诱导的内毒素血症小鼠模型中,治疗可提高存活率并防止器官损伤。CS-E19-mer直接与 LPS 攻击小鼠血浆中的循环组蛋白相互作用。CS-E 19-mer不显示抗凝活性,也不与从患者体内分离出的肝素诱导的血小板减少症抗体发生反应。CS-E 寡糖的成功合成为推进 CS-E 研究提供了结构明确的碳水化合物,并为治疗危及生命的全身性炎症提供了潜在的治疗剂。
更新日期:2020-07-22
down
wechat
bug