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Chemo-enzymatic synthesis and in vitro cytokine profiling of tailor-made oligofructosides

机译:量身定制的低聚果糖苷的化学酶法合成和体外细胞因子谱分析

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Background It is well known that carbohydrates play fundamental roles in cell signaling and infection processes as well as tumor formation and progression. However, the interaction pathways and cellular receptors targeted by carbohydrates and glycoconjugates remain poorly examined and understood. This lack of research stems, at least to a major part, from accessibility problems of large, branched oligosaccharides. Results To test glycan - cell interactions in vitro , a variety of tailored oligosaccharides was synthesized chemo-enzymatically. Glycosyltransferases from the GRAS organisms Bacillus megaterium (SacB) and Aspergillus niger (Suc1) were used in this study. Substrate engineering of these glycosyltransferases generally acting on sucrose leads to the controlled formation of novel tailored di-, tri- and tetrasaccharides. Already industrially used as prebiotics in functional food, the immunogenic potential of novel oligosaccharides was characterized in this study. A differential secretion of CXCL8 and CCL2 was observed upon oligosaccharide co-cultivation with colorectal epithelial Caco-2 cells. Conclusion Pure carbohydrates are able to stimulate a cytokine response in human endothelial cells in vitro . The type and amount of cytokine secretion depends on the type of co-cultivated oligosaccharide.
机译:背景技术众所周知,碳水化合物在细胞信号传导和感染过程以及肿瘤形成和进展中起着基本作用。然而,碳水化合物和糖结合物靶向的相互作用途径和细胞受体仍然缺乏检查和了解。缺乏研究至少在很大程度上是由于大的分支寡糖的可及性问题。结果为了在体外测试聚糖-细胞相互作用,化学-酶促合成了各种定制的寡糖。本研究使用了来自GRAS生物的巨大芽孢杆菌(SacB)和黑曲霉(Suc1)的糖基转移酶。这些通常作用于蔗糖的糖基转移酶的底物工程化导致新型特制的二糖,三糖和四糖的受控形成。这项工业研究已经工业上用作功能食品中的益生元,新型寡糖具有潜在的免疫原性。寡糖与结直肠上皮Caco-2细胞共培养后,观察到CXCL8和CCL2的分泌差异。结论纯碳水化合物可以体外刺激人内皮细胞的细胞因子反应。细胞因子分泌的类型和数量取决于共培养的寡糖的类型。

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