Robinson Tanisha M, Jicsinszky Laszlo, Karginov Andrei V, Karginov Vladimir A
Innovative Biologics, Inc., Herndon, VA, USA.
Innovative Biologics, Inc., Herndon, VA, USA; Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Turin, Italy.
Int J Pharm. 2017 Oct 15;531(2):714-717. doi: 10.1016/j.ijpharm.2017.07.070. Epub 2017 Jul 25.
Clostridium perfringens epsilon toxin (ETX) is considered as one of the most dangerous potential biological weapons. The goal of this work was to identify inhibitors of ETX using a novel approach for the inactivation of pore-forming toxins. The approach is based on the blocking of the target pore with molecules having the same symmetry as the pore itself. About 200 various β-cyclodextrin derivatives were screened for inhibitors of ETX activity using a colorimetric cell viability assay. Several compounds with dose-dependent activities at low micromolar concentrations have been identified. The same compounds were also able to inhibit lethal toxin of Bacillus anthracis.
产气荚膜梭菌ε毒素(ETX)被认为是最危险的潜在生物武器之一。这项工作的目标是使用一种使成孔毒素失活的新方法来鉴定ETX的抑制剂。该方法基于用与孔本身具有相同对称性的分子来阻断目标孔。使用比色细胞活力测定法筛选了约200种不同的β-环糊精衍生物作为ETX活性的抑制剂。已鉴定出几种在低微摩尔浓度下具有剂量依赖性活性的化合物。相同的化合物也能够抑制炭疽芽孢杆菌的致死毒素。