Novel and efficient synthetic inhibitors of anthrax lethal factor
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چکیده
The Burnham Institute, Cancer Research Center and Infectious and Inflammatory Disease Center, 10901 North Torrey Pines Road, La Jolla, CA 92037 The Scripps Research Institute, Molecular Biology, 10550 North Torrey Pines Rd., La Jolla, CA 92037 Dr. Ken Alibek, National Center for Biodefense, George Mason University 10900 University Blvd., PWII Bldg Room-160, MSN 1A8, Manassas, VA 20110, Advanced Biosystems, 5904 Richmond Highway, Suite 300, Alexandria, VA 22303 These authors contributed equally to this work Correspondent author: Maurizio Pellecchia, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037; Tel.: 858-6463159; Fax: 858-713-9925; Email:[email protected]
منابع مشابه
Efficient synthetic inhibitors of anthrax lethal factor.
Inhalation anthrax is a deadly disease for which there is currently no effective treatment. Bacillus anthracis lethal factor (LF) metalloproteinase is an integral component of the tripartite anthrax lethal toxin that is essential for the onset and progression of anthrax. We report here on a fragment-based approach that allowed us to develop inhibitors of LF. The small-molecule inhibitors we hav...
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The lethal factor of Bacillus anthracis is central to the pathogenesis of anthrax. Its mechanism of action is still unknown. Recently, on the basis of sequence similarities, we suggested that lethal factor might act similarly to leukotriene A4 hydrolase (LTA4), a bifunctional enzyme also endowed with a metallopeptidase activity. Here we show that some inhibitors of the LTA4 hydrolase and metall...
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Cell surface proteolytic processing of anthrax protective antigen by furin or other furin-related proteases is required for its oligomerization, endocytosis, and function as a translocon for anthrax lethal and edema factors. Countering toxin lethality is essential to developing effective chemotherapies for anthrax infections that have proceeded beyond the stage at which antibiotics are effectiv...
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The anthrax lethal factor (LF) has a major role in the development of anthrax. LF is delivered by the protective antigen (PA) inside the cell, where it exerts its metalloprotease activity on the N-terminus of MAPK-kinases. PA+LF are cytotoxic to macrophages in culture and kill the Fischer 344 rat when injected intravenously. We describe here the properties of some polyphenols contained in green...
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Anthrax toxin is the major virulence factor produced by Bacillus anthracis. The toxin consists of three protein subunits: protective antigen (PA), lethal factor, and edema factor. Inhibition of PA binding to its receptors, tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2) can effectively block anthrax intoxication, which is particularly valuable when the toxin has a...
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تاریخ انتشار 2005