Synthesis of peptidoglycan fragments and evaluation of their biological activity
Synthesis of peptidoglycan fragments and evaluation of their biological activity
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DOI：
10.1039/b511866b
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发表时间：
2006-01-21
影响因子：
3.2
通讯作者：
Fukase, K
中科院分区：
文献类型：
--
作者：
Inamura, S;Fujimoto, Y;Fukase, K
肽聚糖（PG）细菌细胞壁糖缀合物已被熟知为强免疫增强剂。化学合成了PG的部分结构，以阐明其确切的生物活性。PG的不同重复聚糖的有效构建是通过关键二糖葡糖氨基-β（1-4）-胞壁酸单元的偶联来完成的。二糖单元的立体选择性糖基化通过N-Troc（Troc 2，2，= 2-三氯乙氧羰基）基团的相邻基团参与和N-Troc-葡糖胺基三氯乙酰亚胺酯的适当反应性来实现。通过使用有效的合成策略，以高产率合成了PG的单糖、二糖、四糖和八糖片段。通过诱导来自人单核细胞的肿瘤坏死因子-α（TNF-α）以及通过使用转染的HEK 293细胞的Toll样受体2（TLR 2）和Nod 2依赖性来评估PG的合成片段的生物活性。在这里，我们发现，TLR 2是不刺激的一系列合成PG部分结构，而Nod 2识别含有MDP部分的部分结构。
The peptidoglycan (PG) bacterial cell wall glycoconjugate has been well known as a strong immunopotentiator. Partial structures of PG were chemically synthesized for elucidation of precise biological activities. Effective construction of distinct repeating glycans of PG was accomplished by the coupling of a key disaccharide glucosaminyl-beta(1-4)-muramic acid unit. Stereoselective glycosylation of disaccharide units was achieved by neighboring group participation of the N-Troc (Troc 2,2,= 2-trichloroethoxycarbonyl) group and appropriate reactivity of N-Troc-glucosaminyl trichloroacetimidate. By using an efficient synthetic strategy, mono-, di-, tetra- and octasaccharide fragments of PG were synthesized in high yields. The biological activity of synthetic fragments of PG was evaluated by induction of tumor necrosis factor-alpha (TNF-alpha) from human monocytes, and toll-like receptor 2 (TLR2) and Nod2 dependencies by using transfected HEK293 cells, respectively. Here we reveal that TLR2 was not stimulated by the series of synthetic PG partial structures, whereas Nod2 recognizes the partial structures containing the MDP moiety.