PA-binding domain of LF (LFn) or PA-binding domain of EF (EFn) is the anthrax protective antigen (PA) binding domain of anthrax lethal factor (LF) or edema factor (EF). Here we show the development of a novel anthrax toxin inhibitor, fusion protein of N-terminal 27 amino acids deletion of LFn (Delta27LFn) and EFn. In a cell model of intoxication, fusion protein of Delta27LFn and EFn (Delta27LFn-EFn) was a 62-fold more potent toxin inhibitor than LFn or EFn, and this increased activity corresponded to a 39-fold higher PA-binding affinity by Biacore analysis. More importantly, Delta27LFn-EFn could protect the highly susceptible Fischer 344 rats from anthrax lethal toxin challenge. This work suggested that Delta27LFn-EFn has the potential as a candidate therapeutic agent against anthrax.

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http://dx.doi.org/10.1016/j.febslet.2009.03.053DOI Listing

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