Synthesis of Biotin-Tagged Chitosan Oligosaccharides and Assessment of Their Immunomodulatory Activity.
Synthesis of Biotin-Tagged Chitosan Oligosaccharides and Assessment of Their Immunomodulatory Activity.
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DOI：
10.3389/fchem.2020.554732
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发表时间：
2020
影响因子：
5.5
通讯作者：
Nifantiev NE
中科院分区：
文献类型：
--
作者：
Tsvetkov YE;Paulovičová E;Paulovičová L;Farkaš P;Nifantiev NE
几丁质是一种β-（1→4）-连接的N-乙酰-D-葡萄糖胺聚合物，是真菌细胞壁的主要多糖成分之一。它的N-脱乙酰化形式，壳聚糖，是由几丁质脱乙酰酶在细胞壁中酶促产生的。它发挥免疫调节、抗炎、抗癌、抗菌和抗真菌活性，具有各种医学应用。为了研究壳寡糖的免疫生物学特性，我们合成了一系列β-（1→4）-连接的N-乙酰基-D-葡萄糖胺寡聚体，这些寡聚体包含3，5，7个单糖单元，并带有生物素标签。用于寡糖链延长的关键合成中间体，二糖硫代糖苷，通过4-OH硫代糖苷受体与带有临时4-O-叔丁基二甲基甲硅烷基的糖基三氯乙酰亚胺酯的正交糖基化制备。甲硅烷基保护的使用抑制糖苷配基转移，并提供了一个高产率的目标二糖供体。使用合成的壳聚糖低聚物，以及先前获得的甲壳素对应物，这些合成的寡糖和RAW 264.7细胞之间的免疫生物学关系进行了研究，在体外。对细胞增殖、吞噬作用、呼吸爆发和Th 1、Th 2、Th 17和Treg极化细胞因子表达的评价表明，暴露于几丁质和壳聚糖衍生寡糖的RAW 264.7细胞具有有效的免疫应答和免疫调节作用。巨噬细胞的反应性伴随着显着的诱导剂量和结构依赖性的保护性Th 1和Th 17极化，这是更大的暴露于壳聚糖，而不是几丁质衍生的寡糖。此外，没有观察到抗增殖或细胞毒性作用，即使在延长48小时的接触。所获得的结果表明，这些合成制备的壳寡糖的有效的免疫生物活性。
Chitin, a polymer of β-(1→4)-linked N-acetyl-d-glucosamine, is one of the main polysaccharide components of the fungal cell wall. Its N-deacetylated form, chitosan, is enzymatically produced in the cell wall by chitin deacetylases. It exerts immunomodulative, anti-inflammatory, anti-cancer, anti-bacterial, and anti-fungal activities with various medical applications. To study the immunobiological properties of chitosan oligosaccharides, we synthesized a series of β-(1→4)-linked N-acetyl-d-glucosamine oligomers comprising 3, 5, and 7 monosaccharide units equipped with biotin tags. The key synthetic intermediate employed for oligosaccharide chain elongation, a disaccharide thioglycoside, was prepared by orthogonal glycosylation of a 4-OH thioglycoside acceptor with a glycosyl trichloroacetimidate bearing the temporary 4-O-tert-butyldimethylsilyl group. The use of silyl protection suppressed aglycon transfer and provided a high yield for the target disaccharide donor. Using synthesized chitosan oligomers, as well as previously obtained chitin counterparts, the immunobiological relationship between these synthetic oligosaccharides and RAW 264.7 cells was studied in vitro. Evaluation of cell proliferation, phagocytosis, respiratory burst, and Th1, Th2, Th17, and Treg polarized cytokine expression demonstrated effective immune responsiveness and immunomodulation in RAW 264.7 cells exposed to chitin- and chitosan-derived oligosaccharides. Macrophage reactivity was accompanied by significant inductive dose- and structure-dependent protective Th1 and Th17 polarization, which was greater with exposure to chitosan- rather than chitin-derived oligosaccharides. Moreover, no antiproliferative or cytotoxic effects were observed, even following prolonged 48 h exposure. The obtained results demonstrate the potent immunobiological activity of these synthetically prepared chito-oligosaccharides.
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影响因子：
4.4
作者：
Da Silva, Carla A.;Chalouni, Cecile;Elias, Jack A.
通讯作者：
Elias, Jack A.
DOI：
10.3390/molecules22030429
发表时间：
2017-03-08
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Tanaka H;Hamaya Y;Kotsuki H
通讯作者：
Kotsuki H
DOI：
10.1164/rccm.200912-1877oc
发表时间：
2010-12-15
影响因子：
24.7
作者：
Da Silva, Carla A.;Pochard, Pierre;Elias, Jack A.
通讯作者：
Elias, Jack A.
影响因子：
3.1
作者：
Cartmell, Jonathan;Paszkiewicz, Eugenia;Bundle, David R.
通讯作者：
Bundle, David R.
影响因子：
3.2
作者：
Dang, Anh-Thu;Johnson, Margaret A.;Bundle, David R.
通讯作者：
Bundle, David R.