E5531, A PURE ENDOTOXIN ANTAGONIST OF HIGH POTENCY
E5531, A PURE ENDOTOXIN ANTAGONIST OF HIGH POTENCY
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DOI：
10.1126/science.7701344
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发表时间：
1995-04-07
期刊：
影响因子：
56.9
通讯作者：
YAMATSU, I
中科院分区：
文献类型：
--
作者：
CHRIST, WJ;ASANO, O;YAMATSU, I
革兰氏阴性细菌败血症所致休克是细菌释放的内毒素或内毒素引起的急性炎症反应的结果。脂多糖是革兰氏阴性细菌外膜的主要成分，其末端二糖磷脂(脂A)部分含有与毒性活性有关的关键结构特征。基于所提出的无毒胶囊红杆菌脂类A的结构，合成了一种完全稳定的内毒素拮抗剂E5531。在体外，E5531在多种系统中表现出强烈的拮抗内毒素介导的细胞激活作用。在体内，E5531保护小鼠免受内毒素诱导的死亡，并与抗生素合作，保护小鼠免受存活的大肠杆菌的致命感染。
Shock due to Gram-negative bacterial sepsis is a consequence of acute inflammatory response to lipopolysaccharide (LPS) or endotoxin released from bacteria. LPS is a major constituent of the outer membrane of Gram-negative bacteria, and its terminal disaccharide phospholipid (lipid A) portion contains the key structural features responsible for toxic activity. Based on the proposed structure of nontoxic Rhodobacter capsulatus lipid A, a fully stabilized endotoxin antagonist E5531 has been synthesized. In vitro, E5531 demonstrated potent antagonism of LPS-mediated cellular activation in a variety of systems. In vivo, E5531 protected mice from LPS-induced lethality and, in cooperation with an antibiotic, protected mice from a lethal infection of viable Escherichia coli.