Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Anthrax inhibitors identified by Burnham team

22.06.2005


Novel and efficient inhibitors of anthrax lethal factor 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 alone.

"This represents a significant advance in developing a possible emergency treatment for anthrax," said Dr. Pellecchia. "We are working on refining the chemical structure of the compound with the goal of achieving an even more potent and selective drug that should exhibit a higher degree of protection against anthrax."

This research was supported by grants from the National Institute of Allergy and Infectious Diseases, from the National Institutes of Health.

Coauthors on this study include:

Martino Forino, Sherida Johnson, Tian Y. Wong, Dimitri V. Rozanov, Alexei Y. Savinov, Wei Li, Roberto Fattorusso, Barbara Becattini, and Dawoon Jung, from The Burnham Institute.
Robert Liddington, Ph.D., Acting Director, Center for Infectious and Inflammatory Diseases at The Burnham Institute;
Alex Strongin, Ph.D., Professor, Cell Adhesion/Extracellular Matrix Program, The Burnham Institute;
Jeffrey Smith, Ph.D., Professor, and Director of the Center for Proteolytic Pathways at The Burnham Institute;
Ruben A. Abagyan, Ph.D., Professor, and Andrew J. Orry, Molecular Biology Department at The Scripps Research Institute;
Ken Alibek, Ph.D., National Center for Biodefense, George Mason University, Fairfax, Virginia.

Nancy Beddingfield | EurekAlert!
Further information:
http://www.burnham.org

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Speed data for the brain’s navigation system

06.12.2016 | Health and Medicine

What happens in the cell nucleus after fertilization

06.12.2016 | Life Sciences

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>