Tanamoto K
National Institute of Health Sciences, Tokyo, Japan.
FEBS Lett. 1994 Sep 12;351(3):325-9. doi: 10.1016/0014-5793(94)00857-4.
The synthetic disaccharide precursor of lipid A (406: identical to lipid IVA) was found to reduce its endotoxic activity in mice by an order of 10(5) or more, by replacing the hydroxyl groups with succinyl or acetyl residues. Both the succinylated and acetylated 406 were also found to antagonize the endotoxic mitogenicity on murine splenocytes. Previous studies demonstrated that the succinylated or acetylated synthetic complete lipid A preparations retained the whole endotoxic activity [1994, Infect. Immunol. 62, 1705]. The drastic contrast in all of these results suggests the importance of the substituents on the hydroxyl groups of 3-hydroxy fatty acids of non-reducing glucosamine of lipid A for the activity and for transformation to the antagonistic structure.
脂质A的合成二糖前体（406：等同于脂质IVA）被发现可使小鼠体内的内毒素活性降低10⁵倍或更多，方法是用琥珀酰基或乙酰基残基取代羟基。琥珀酰化和乙酰化的406还被发现可拮抗对小鼠脾细胞的内毒素促有丝分裂活性。先前的研究表明，琥珀酰化或乙酰化的合成完整脂质A制剂保留了全部内毒素活性[1994年，《感染与免疫》62卷，第1705页]。所有这些结果的巨大反差表明，脂质A非还原葡糖胺的3-羟基脂肪酸羟基上的取代基对于活性以及转化为拮抗结构具有重要意义。
