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关于免疫刺激皂素 - 脂质复合物(免疫刺激复合物,iscoms)的结构

On the structure of immune-stimulating saponin-lipid complexes (iscoms).

作者信息

Kersten G F, Spiekstra A, Beuvery E C, Crommelin D J

机构信息

Department of Inactivated Viral Vaccines, National Institute for Public Health and Environmental Protection (RIVM), Bilthoven, The Netherlands.

出版信息

Biochim Biophys Acta. 1991 Feb 25;1062(2):165-71. doi: 10.1016/0005-2736(91)90388-o.

DOI:10.1016/0005-2736(91)90388-o
PMID:2004105
Abstract

Immune-stimulating complexes (iscoms) are stable complexes of cholesterol, phospholipid and Quil A, a triterpene saponin mixture in the size range from 40 to 100 nm. They can be used as antigen carriers in subunit vaccines. In this paper it is demonstrated that iscoms are rigid, negatively charged vesicles in which small water soluble molecules like carboxyfluorescein cannot be retained. The negative zeta-potential prevents iscoms from aggregation. The chemical composition of iscoms in one dispersion varied considerably. A typical example of the composition of iscoms is cholesterol/phospholipid/Quil A = 1.0:1.2:6.2 by weight for the iscom matrix, that is iscoms without antigen, and 1.0:1.3:5.1 for antigen-containing iscoms. A hypothetical model for the structure of the iscom matrix and related structures is presented, based on analytical chemical, physico-chemical and electronmicroscopic data. In this model iscoms are considered to be multi-micellar structures, shaped and stabilized by hydrophobic interactions, electrostatic repulsion, steric factors and possibly hydrogen bonds. The individual micelles are relatively flat, ring-shaped structures, the center offering space for one of the two bulky sugar chains of the saponins.

摘要

免疫刺激复合物(iscoms)是胆固醇、磷脂和皂树毒素A(一种三萜皂苷混合物)的稳定复合物,大小在40至100纳米之间。它们可用作亚单位疫苗中的抗原载体。本文证明,iscoms是刚性的带负电荷的囊泡,其中像羧基荧光素这样的小水溶性分子无法保留。负的ζ电位可防止iscoms聚集。一种分散体中iscoms的化学成分差异很大。iscoms组成的一个典型例子是,对于iscom基质(即不含抗原的iscoms),胆固醇/磷脂/皂树毒素A的重量比为1.0:1.2:6.2,对于含抗原的iscoms,该比例为1.0:1.3:5.1。基于分析化学、物理化学和电子显微镜数据,提出了iscom基质及相关结构的假设模型。在该模型中,iscoms被认为是多胶束结构,通过疏水相互作用、静电排斥、空间因素以及可能的氢键形成并稳定。单个胶束是相对扁平的环形结构,其中心为皂苷的两条大糖链之一提供空间。

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