INFLUENCE OF THE SUPRAMOLECULAR STRUCTURE OF FREE LIPID-A ON ITS BIOLOGICAL-ACTIVITY
INFLUENCE OF THE SUPRAMOLECULAR STRUCTURE OF FREE LIPID-A ON ITS BIOLOGICAL-ACTIVITY
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DOI：
10.1111/j.1432-1033.1993.tb18409.x
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发表时间：
1993-12-01
期刊：
影响因子：
--
通讯作者：
SEYDEL, U
中科院分区：
文献类型：
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作者：
BRANDENBURG, K;MAYER, H;SEYDEL, U
利用同步辐射x射线衍射和傅里叶变换红外光谱研究了不同革兰氏阴性种脂质A在40℃、高含水量（80-90%）和不同[脂质A]/[Mg2+]摩尔比下的三维超分子结构和酰基链的序态。测定明尼苏达沙门氏菌R595、单磷和双磷的游离脂质A，以及荚膜红杆菌37b4、绿红假单胞菌F和明胶红环菌29/1的游离脂质A。非肠杆菌类脂质A与肠杆菌类脂质A在37℃的结构多态性和有序状态也存在差异，其超分子结构与先前确定的生物活性之间存在明显的相关性。脂质A具有强烈的层状结构偏好(Rb。荚膜和Rp。病毒不具有内毒活性，缺乏细胞因子诱导能力；具有混合层状/非层状结构的化合物（来自明尼苏达州的单磷酰脂质a）在体内毒性较低，但在体外可能诱导细胞因子：具有强烈倾向于形成非层状倒置结构的脂质a（来自明尼苏达州和Rc的脂质a）。明胶菌在体内和体外均表现出充分的内毒素。相反，具有层状结构的化合物的抗互补活性最为明显，而具有反转结构的化合物的抗互补活性表达最少。37℃时的顺序状态无系统变化，脂质A最高，Rc最低。gelatinosus。我们建议将术语“内毒构象”（用于描述最佳触发生物效应所需的单个脂质a分子的构象）扩展为“内毒超分子构象”（表示生理液体中引起生物活性的脂质a聚集的特定组织）。
The three-dimensional supramolecular structures and the states of order of the acyl chains of lipid A from different Gram-negative species were investigated at 40-degrees-C, high water content (80-90%), and different [lipid A]/[Mg2+] molar ratios using synchrotron radiation X-ray diffraction and Fourier-transform infrared spectroscopy. Measurements were made on free lipid A from Salmonella minnesota R595, mono- and bi-phosphoryl, as well as those from the non-enterobacterial strains Rhodobacter capsulatus 37b4, Rhodopseudomonas viridis F, and Rhodocyclus gelatinosus 29/1. Parallel to differences in their chemical primary structure, the structural polymorphisms and states of order at 37-degrees-C of the non-enterobacterial lipid A were found to be different from those of enterobacterial lipid A. A clear correlation between the supramolecular structure and previously determined biological activities was found. Lipid A with a strong preference for lamellar structures (Rb. capsulatus and Rp. viridis) are endotoxically inactive and lack cytokine-inducing capacity; the compounds assuming a mixed lamellar/nonlamellar structure (monophosphoryl lipid A from S. minnesota) are of lower toxicity in vivo, but may induce cytokines in vitro: those lipid A with a strong tendency to form non-lamellar inverted structures (lipid A from S. minnesota and Rc. gelatinosus) exhibit full endotoxicity in vitro and in vivo. In contrast, anti-complementary activity is most pronounced for compounds with lamellar and least expressed for those with inverted structures. The states of order at 37-degrees-C vary non-systematically, exhibiting the highest values for lipid A of S. minnesota and the lowest for that of Rc. gelatinosus.We propose to extend the term 'endotoxic conformation', which is used to describe the conformation of a single lipid A molecule required for optimal triggering of biological effects, to 'endotoxic supramolecular conformation' which denotes the particular organization of lipid A aggregates in physiological fluids causing biological activity.