Mechanism of anti-HIV activity of negatively charged albumins: Biomolecular interaction with the HIV-1 envelope protein gp120
Mechanism of anti-HIV activity of negatively charged albumins: Biomolecular interaction with the HIV-1 envelope protein gp120
复制标题
DOI：
10.1097/00042560-199604150-00001
复制
发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Meijer, DKF
中科院分区：
文献类型：
--
作者：
Kuipers, ME;Huisman, JG;Meijer, DKF
一类新的多阴离子蛋白具有有效的抗人类免疫缺陷病毒1型活性，即负电荷白蛋白（NCAs），以前已经报道过。体外抗病毒试验证实，这些化合物优先抑制病毒-细胞融合和合胞体形成，病毒-细胞结合受到的影响较小。本文描述了NCAs与由15-36个氨基酸组成的合成肽的相互作用，这些肽对应于gp120包膜蛋白的不同部分。在测试的gp120肽中，NCAs仅与所谓的V3环（氨基酸296-330）和gp120的c端部分结合。白蛋白中带负电荷残基的数量越多，结合亲和力越高。在NCAs中，除了负电荷外，分别引入多达7个或14个乳糖或甘露糖基团，并没有表现出增加的结合亲和力。相比之下，含有约14个甘露糖基团的甘露糖化白蛋白与天然白蛋白的结合增加。硫酸化多糖肝素和硫酸葡聚糖竞争性地抑制了NCAs与V3和c端寡肽的结合。这一发现表明gp120肽与NCAs之间的结合可能是由静电相互作用引起的。然而，与NCAs相比，硫酸葡聚糖和肝素的解离常数要大几个数量级，这表明蛋白质的空间结构和/或NCAs与包膜蛋白之间的疏水相互作用也可能参与其中。
A novel class of polyanionic proteins with potent anti-human immunodeficiency virus type 1 activity, the negatively charged albumins (NCAs), have been reported previously. In vitro antiviral assays established that these compounds preferentially inhibit virus-cell fusion and syncytium formation and that virus-cell binding is less affected. Here the interaction of the NCAs with synthetic peptides composed of 15-36 amino acids and corresponding to different parts of the gp120 envelope protein is described. Among the gp120 peptides tested, binding of the NCAs was observed only with the so-called V3 loop (amino acids 296-330) and the C-terminal part of gp120. A higher number of negatively charged residues in the albumins resulted in higher binding affinities. NCAs in which, in addition to negative charges, up to 7 or 14 lactose or mannose groups were introduced, respectively, did not exhibit increasing binding affinity. In contrast, mannosylated albumin containing about 14 mannose groups showed an increased binding compared with native albumin. Binding of the NCAs to the V3 and C-terminal oligopeptide was competitively inhibited by sulfated polysaccharide heparin and dextran sulfate. This finding indicates that the binding between the gp120 peptides and the NCAs is likely caused by electrostatic interactions. However, the fact that the dissociation constants of dextran sulfate and heparin are orders of magnitude larger compared with the NCAs indicates that the spatial structure of the proteins and/or hydrophobic interactions between the NCAs and the envelope protein may also be involved.