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Inhibition of the proteolytic activity of anthrax lethal factor by aminoglycosides
Lac V Lee1, Kristen E Bower, Fu-Sen Liang
1Department of Chemistry and the Skaggs Institute for Chemical Biology, La Jolla, California 92037, USA.
Abstract:
The anthrax lethal factor (LF), a Zn-dependent endopeptidase, is considered the dominant virulence factor of anthrax. Because pharmacological inhibition of the catalytic activity of LF is considered a plausible mechanism for preventing the lethality of anthrax, a high-throughput screening experiment based on LF-catalyzed cleavage of a fluorescent substrate was performed to identify novel inhibitors of LF. The RNA-targeting antibiotics, neomycin B and some synthetic dimeric aminoglycosides, were found to be nanomolar active-site inhibitors of LF.
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