title: Small molecule inhibitors of anthrax toxin-induced cytotoxicity targeted against protective antigen.
abstract: Two molecular scaffolds were designed using the CAVEAT molecular design package to inhibit the oligomerization of protective antigen (PA(63) ), a key protein component of anthrax toxin. The inhibitors were designed to prevent heptamerization of PA(63)  by mimicking key residues of PA(63)  needed for the intermolecular interactions that stabilize the heptamer. Using the scaffolds identified by CAVEAT, seven candidate inhibitors were synthesized and tested for their ability to inhibit anthrax toxin-induced cytotoxicity, with three of the agents demonstrating modest inhibition in murine J774A.1 macrophage cells.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Rubert Pérez
authors.forename: Daneli
authors.initials: D
authors.lastname: López-Pérez
authors.forename: Jean
authors.initials: J
authors.lastname: Chmielewski
authors.forename: Mark
authors.initials: M
authors.lastname: Lipton
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism / Q000633:toxicity; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D002478:Cells, Cultured; D015195:Drug Design; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D025941:Protein Interaction Mapping; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D054852:Small Molecule Libraries; C030325:anthrax toxin