牙龈卟啉单胞菌脂多糖A的合成四酰化衍生物是人类Toll样受体4的拮抗剂。
Synthetic tetra-acylated derivatives of lipid A from Porphyromonas gingivalis are antagonists of human TLR4.
作者信息
Zhang Yanghui, Gaekwad Jidnyasa, Wolfert Margreet A, Boons Geert-Jan
机构信息
Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
出版信息
Org Biomol Chem. 2008 Sep 21;6(18):3371-81. doi: 10.1039/b809090d. Epub 2008 Jul 25.
Abstract
Tetra-acylated lipid As derived from Porphyromonas gingivalis LPS have been synthesized using a key disaccharide intermediate functionalized with levulinate (Lev), allyloxycarbonate (Alloc) and anomeric dimethylthexylsilyl (TDS) as orthogonal protecting groups and 9-fluorenylmethoxycarbamate (Fmoc) and azido as amino protecting groups. Furthermore, an efficient cross-metathesis has been employed for the preparation of the unusual branched R-(3)-hydroxy-13-methyltetradecanic acid and (R)-3-hexadecanoyloxy-15-methylhexadecanoic acid of P. gingivalis lipid A. Biological studies have shown that the synthetic lipid As cannot activate human and mouse TLR2 and TLR4 to produce cytokines. However, it has been found that the compounds are potent antagonist of cytokine secretion by human monocytic cells induced by enteric LPS.
摘要
源自牙龈卟啉单胞菌脂多糖的四酰化脂质A已通过使用一种关键的二糖中间体合成，该中间体用乙酰丙酸酯（Lev）、烯丙基碳酸酯（Alloc）和异头二甲基叔丁基硅烷基（TDS）作为正交保护基，以及9-芴甲氧羰基（Fmoc）和叠氮基作为氨基保护基进行功能化。此外，已采用高效交叉复分解反应制备牙龈卟啉单胞菌脂质A中不寻常的支链R-(3)-羟基-13-甲基十四烷酸和(R)-3-十六烷酰氧基-15-甲基十六烷酸。生物学研究表明，合成的脂质A不能激活人和小鼠的TLR2和TLR4以产生细胞因子。然而，已发现这些化合物是肠道脂多糖诱导的人单核细胞分泌细胞因子的有效拮抗剂。
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