Exploring the Nature of Cationic Blocker Recognition by the Anthrax Toxin Channel.

Obstructing conductive pathways of the channel-forming toxins with targeted blockers is a promising drug design approach. Nearly all tested positively charged ligands have been shown to reversibly block the cation-selective channel-forming protective antigen (PA) component of the binary anthrax toxin. The cationic ligands with more hydrophobic surfaces, particularly those carrying aromatic moieties, inhibited PA more effectively.

Inhibition of Clostridium perfringens epsilon toxin by β-cyclodextrin derivatives.

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.

Tailored cyclodextrin pore blocker protects mammalian cells from clostridium difficile binary toxin CDT.

Some Clostridium difficile strains produce, in addition to toxins A and B, the binary toxin Clostridium difficile transferase (CDT), which ADP-ribosylates actin and may contribute to the hypervirulence of these strains. The separate binding and translocation component CDTb mediates transport of the enzyme component CDTa into mammalian target cells. CDTb binds to its receptor on the cell surface, CDTa assembles and CDTb/CDTa complexes are internalised.

Cationic quaternized aminocalix[4]arenes: cytotoxicity, haemolytic and antibacterial activities.

This study reports the characterization of three cationic amphiphillic aminocalix[4]arenes as potential antimicrobial agents in vitro. In cytotoxicity tests on mouse macrophage RAW 264.7 cells aminocalix[4]arenes 1 and 3 showed no toxicity up to 200 and 100 μM concentrations, respectively, while 2 was non-toxic only up to 50 μM.

Cyclodextrin derivatives as anti-infectives.

Cyclodextrin derivatives can be utilized as anti-infectives with pore-forming proteins as the targets. The highly efficient selection of potent inhibitors was achieved because per-substituted cyclodextrins have the same symmetry as the target pores. Inhibitors of several bacterial toxins produced by Bacillus anthracis, Staphylococcus aureus, Clostridium perfringens, Clostridium botulinum, and Clostridium difficile were identified from a library of ∼200 CD derivatives.