The overall goal of this SBIR proposal is the identification of small molecules capable of blocking the cytotoxic action of Bacillus anthracis lethal toxin by blocking the transmembrane pore formed by the protective antigen component of the toxin. Such molecules are envisioned for use as drugs for the treatment of anthrax. The strategy to identify such compounds involves developing an assay for testing the ability of compounds to inhibit the cytotoxic effect of anthrax toxin. A limited representative library of compounds will be designed and synthesized. The synthesized compounds will then be tested for inhibitory activity. The resulting baseline data will be used for computer-assisted design of compounds with improved affinity towards the transmembrane pore, followed by a second round of chemical synthesis and testing.
| Karginov, Vladimir A (2013) Cyclodextrin derivatives as anti-infectives. Curr Opin Pharmacol 13:717-25 |
| Karginov, Vladimir A; Yohannes, Adiamseged; Robinson, Tanisha M et al. (2006) Beta-cyclodextrin derivatives that inhibit anthrax lethal toxin. Bioorg Med Chem 14:33-40 |
| Karginov, Vladimir A; Nestorovich, Ekaterina M; Moayeri, Mahtab et al. (2005) Blocking anthrax lethal toxin at the protective antigen channel by using structure-inspired drug design. Proc Natl Acad Sci U S A 102:15075-80 |
