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α-葡萄糖基二酰基甘油的合成作为肺炎链球菌疫苗的潜在佐剂。

Synthesis of α-Glucosyl Diacylglycerides as potential adjuvants for Streptococcus pneumoniae vaccines.

机构信息

School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, Wellington, New Zealand; Centre for Biodiscovery, Victoria University of Wellington, P. O. Box 600, Wellington, 6140, New Zealand.

Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany; German Center for Lung Research, partner site BREATH, Hannover, Germany.

出版信息

Carbohydr Res. 2020 Mar;489:107951. doi: 10.1016/j.carres.2020.107951. Epub 2020 Feb 13.

Abstract

α-Glucosyl diacylglycerols (αGlc-DAGs) play an important role in providing protective immunity against Streptococcus pneumoniae infection through the engagement of the Macrophage inducible C-type lectin (Mincle). Herein, we efficiently synthesised αGlc-DAGs containing C12, C14, C16 and C18 acyl chains in 7 steps and 44-47% overall yields, and demonstrated that Mincle signaling was dependent on lipid length using mMincle and hMincle NFAT-GFP reporter cells. The greatest production of GFP in both cell types was elicited by C14 αGlc-DAG. Accordingly, C14 αGlc-DAG has potential to act as an adjuvant to augment the immune response against S. pneumoniae antigens.

摘要

α-葡萄糖基二酰基甘油(αGlc-DAGs)通过与巨噬细胞诱导型 C 型凝集素(Mincle)结合,在提供针对肺炎链球菌感染的保护性免疫方面发挥着重要作用。在此,我们通过 7 步反应以 44-47%的总收率高效合成了含有 C12、C14、C16 和 C18 酰基链的αGlc-DAGs,并通过 mMincle 和 hMincle NFAT-GFP 报告细胞证实了 Mincle 信号转导依赖于脂质长度。两种细胞类型中 GFP 产量最大的是 C14αGlc-DAG。因此,C14αGlc-DAG 具有作为佐剂增强针对肺炎链球菌抗原的免疫应答的潜力。

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