Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
Org Biomol Chem. 2013 Aug 14;11(30):5034-41. doi: 10.1039/c3ob40899j. Epub 2013 Jun 26.
An extreme thermophile, Thermus thermophilus, has very unique glycolipids on the cell surface. The acidic immunostimulatory phosphoglycolipid of T. thermophilus was synthesized for the first time, with newly developed glycosylation methods using 3-nitropyridyl (3NPy) and 4,6-dimethoxy-1,3,5-triazin-2-yl (DMT) glycosides as glycosyl donors. The analogues of the phosphoglycolipid, which include a diastereomer possessing the opposite configuration at the diacyl glycerol moiety, were also synthesized. The biological activities of the synthesized compounds were elucidated with cytokine inductions (IL-6 and TNF-α). A synthetic phosphoglycolipid with a natural-type diacyl glycerol configuration showed apparent immunostimulatory activity, whereas its diastereomer did not. The present study revealed that the configuration at the diacyl glycerol moiety of the phosphoglycolipids is important for immunostimulation, suggesting the existence of the particular receptor/recognizing protein that can recognize the stereochemistry of the glycerol part.
一种极端嗜热菌，Thermus thermophilus，在其细胞表面具有非常独特的糖脂。首次合成了 Thermus thermophilus 的酸性免疫刺激磷酸糖脂，使用新开发的糖基化方法，使用 3-硝基吡啶（3NPy）和 4,6-二甲氧基-1,3,5-三嗪-2-基（DMT）糖苷作为糖基供体。还合成了该磷酸糖脂的类似物，包括在二酰基甘油部分具有相反构型的非对映异构体。用细胞因子诱导（IL-6 和 TNF-α）阐明了合成化合物的生物学活性。具有天然型二酰基甘油构型的合成磷酸糖脂显示出明显的免疫刺激活性，而其非对映异构体则没有。本研究表明，磷酸糖脂中二酰基甘油部分的构型对于免疫刺激很重要，这表明存在可以识别甘油部分立体化学的特定受体/识别蛋白。
