Cationic polyamines inhibit anthrax lethal factor protease.

摘要: Anthrax is a human disease that results from infection by the bacteria, Bacillus anthracis and has recently been used as bioterrorist agent. Historically, this was associated with spore exposure wool or animal carcasses. While current vaccine approaches (targeted against protective antigen) are effective for prophylaxis, multiple doses must be injected. Common antibiotics block germination process but administered early in cycle. In addition, new therapeutics needed to specifically target proteolytic activity of lethal factor (LF) bacterial infection. Using fluorescence-based assay identify characterize inhibitors anthrax protease activity, we identified several chemically-distinct classes inhibitory molecules including polyamines, aminoglycosides cationic peptides. these studies, spermine demonstrated first time inhibit LF Ki value 0.9 ± 0.09 μM (mean SEM; n = 3). Additional linear polyamines were also active lower potencies. Based upon studies reported herein, chose related potential lead optimization candidates additional testing cell-based models where cell penetration could studied. During our screening process, reproducibly potencies certain compounds, neomycin not neamine spermine, different depending presence absence nucleic acids. Differential sensitivity presence/absence acids may an point consider when comparing various compounds optimization.