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Inhibition of the proteolytic activity of anthrax lethal factor by aminoglycosides

Academic Article
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Overview

related to degree

  • Wu, Douglass, Ph.D. in Chemistry, Scripps Research 2001 - 2006
  • Liang, Fu-Sen, Ph.D. in Chemistry, Scripps Research 2000 - 2005

authors

  • Lee, L. V.
  • Bower, K. E.
  • Liang, Fu-Sen
  • Shi, J.
  • Wu, Douglass
  • Sucheck, S. J.
  • Vogt, Peter K.
  • Wong, Chi-Huey

publication date

  • April 2004

journal

  • Journal of the American Chemical Society  Journal

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.

subject areas

  • Antigens, Bacterial
  • Bacillus anthracis
  • Bacterial Toxins
  • Enzyme Inhibitors
  • Framycetin
  • Mitogen-Activated Protein Kinases
  • Models, Molecular
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Identity

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja0495359

PubMed ID

  • 15080670
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Additional Document Info

start page

  • 4774

end page

  • 4775

volume

  • 126

issue

  • 15

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