ORGN 916 |
| Anthrax, a disease caused by Bacillus anthracis, has come to worldwide attention as a biological weapon in recent years. Anthrax lethal toxin, consisting of protective antigen, lethal factor, and edema factor is the causative agent of anthrax pathogenesis. Recently, agents were identified that rescued cells from anthrax lethal toxin mediated cell death via a medium throughput cell-based screen. Secondary in vitro assays were used to determine the molecular targets of each agent. Compounds were identified that selectively inhibited anthrax lethal factor (LF). An SAR study based upon lethal factor inhibitor N-oleoyldopamine (OLDA, 1) produced additional LF inhibitors with good cell activity and low cellular cytotoxicity. Mechanistic studies identified these compounds as uncompetitive inhibitors with the most potent agent having a Ki value of 1.7 + 0.1 μM. |
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Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
8:00 AM-12:00 PM, Thursday, August 23, 2007 BCEC -- 258B, Oral
Division of Organic Chemistry |
