Inhibition of the proteolytic activity of anthrax lethal factor by aminoglycosides.
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.
Lee
Lac V
LV
Department of Chemistry and the Skaggs Institute for Chemical Biology, La Jolla, California 92037, USA.
Bower
Kristen E
KE
Liang
Fu-Sen
FS
Shi
Jin
J
Wu
Douglass
D
Sucheck
Steven J
SJ
Vogt
Peter K
PK
Wong
Chi-Huey
CH
D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000187:drug effects / Q000201:enzymology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005601:Framycetin / Q000737:chemistry / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; C030325:anthrax toxin; D005601:Framycetin; D020928:Mitogen-Activated Protein Kinases