( A collaborative team of scientists led ...)Anthrax inhibitors identified by Burnham team

A collaborative team of scientists led by The Burnham Institute's Maurizio Pellecchia, Ph.D., has identified inhibitors of the anthrax toxin, termed lethal factor ("LF") that could be developed into an emergency treatment for exposure to inhalation anthrax. These findings will be published by the Proceedings of the National Academy of Sciences by Early Edition at the journal's website the week of June 20th.

Bacillus anthracis ("anthrax") is a proven agent of biological terrorism. Pulmonary anthrax, in which spores of the anthrax bacteria are inhaled, is typically fatal unless diagnosis is made at an early stage of infection, when antibiotics such as Ciprofloxacin can provide a complete cure. At late stages in the disease, antibiotics can kill the anthrax bacteria, but do not affect LF secreted by the bacteria, which is sufficiently concentrated in the bloodstream. LF enters cells and inactivates a human protein called "mitogen-activated protein kinase", or "MAPKK", disrupting the normal signaling pathways of the cell and inducing cell-death.

Using a fragment-based approach based on assays conducted with highly sensitive nuclear magnetic resonance ("NMR") techniques developed in Dr. Pellecchia's laboratory, the scientists were able to identify a scaffold that served as a template for designing a preferred structure for small-molecule inhibitors of LF. Lead compounds were synthesized and validated as highly potent and selective against LF in vitro. In in vitro assays, the compounds did not affect prototype human metalloproteinase enzymes that are structurally similar to LF. This is very important as selectivity is a fundamental prerequisite for a drug to be safe for use in humans.

Three lead compounds where tested in mice infected with anthrax spores, in combination with the antibiotic Ciprofloxacin. The survival rate for mice treated with each of the compounds tested in the combination therapy was two-fold over mice treated with Ciprofloxacin a
'"/>

Source:Burnham Institute

Page: 1 2 3
Related biology news :

1. Study Models Impact Of Anthrax Vaccine
2. Anthrax test, developed by army and CDC, receives FDA approval
3. Anthrax stops body from fighting back, study shows
4. Anthrax spores may survive water treatment
5. Anthrax inhibitor counteracts toxin, may lead to new therapeutics
6. Anthrax attack posed greater potential threat than thought
7. Anthrax paralyzes immune cells with lethal toxin, UF research shows
8. Protease inhibitors reach beyond HIV
9. Enzyme inhibitors block replication of SARS virus
10. Sweet water taste paradoxically predicts sweet taste inhibitors
11. COX-2 inhibitors significantly reduce risk of cancer