Department of Biology, The Catholic University of America, Washington, D.C., 20064, USA.
Curr Top Microbiol Immunol. 2017;406:199-227. doi: 10.1007/82_2016_20.
Rational design of multivalent molecules represents a remarkable modern tool to transform weak non-covalent interactions into strong binding by creating multiple finely-tuned points of contact between multivalent ligands and their supposed multivalent targets. Here, we describe several prominent examples where the multivalent blockers were investigated for their ability to directly obstruct oligomeric channel-forming bacterial exotoxins, such as the pore-forming bacterial toxins and B component of the binary bacterial toxins. We address problems related to the blocker/target symmetry match and nature of the functional groups, as well as chemistry and length of the linkers connecting the functional groups to their multivalent scaffolds. Using the anthrax toxin and AB5 toxin case studies, we briefly review how the oligomeric toxin components can be successfully disabled by the multivalent non-channel-blocking inhibitors, which are based on a variety of multivalent scaffolds.
多价分子的合理设计代表了一种卓越的现代工具，可以通过在多价配体与其假定的多价靶标之间创建多个精细调整的接触点，将弱非共价相互作用转化为强结合。在这里，我们描述了几个突出的例子，其中多价阻滞剂被研究用于其直接阻断寡聚通道形成的细菌外毒素的能力，例如形成孔的细菌毒素和二元细菌毒素的 B 成分。我们解决了与阻滞剂/靶标对称匹配和功能基团性质以及连接功能基团与其多价支架的键的化学性质和长度相关的问题。使用炭疽毒素和 AB5 毒素的案例研究，我们简要回顾了多价非通道阻断抑制剂如何成功地使寡聚毒素成分失活，这些抑制剂基于多种多价支架。
