Bezrukov Sergey M, Nestorovich Ekaterina M
Program in Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Biology, The Catholic University of America, Washington, DC 20064, USA
Pathog Dis. 2016 Mar;74(2). doi: 10.1093/femspd/ftv113. Epub 2015 Dec 9.
Emergent rational drug design techniques explore individual properties of target biomolecules, small and macromolecule drug candidates, and the physical forces governing their interactions. In this minireview, we focus on the single-molecule biophysical studies of channel-forming bacterial toxins that suggest new approaches for their inhibition. We discuss several examples of blockage of bacterial pore-forming and AB-type toxins by the tailor-made compounds. In the concluding remarks, the most effective rationally designed pore-blocking antitoxins are compared with the small-molecule inhibitors of ion-selective channels of neurophysiology.
新兴的合理药物设计技术探索目标生物分子、小分子和大分子候选药物的个体特性,以及控制它们相互作用的物理力。在这篇微型综述中,我们重点关注形成通道的细菌毒素的单分子生物物理研究,这些研究为其抑制提供了新方法。我们讨论了定制化合物阻断细菌成孔毒素和AB型毒素的几个例子。在结论部分,将最有效的合理设计的孔阻断抗毒素与神经生理学中离子选择性通道的小分子抑制剂进行了比较。