Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Johns Hopkins team finds new way to attack TB

25.03.2010
Suspecting that a particular protein in tuberculosis was likely to be vital to the bacteria's survival, Johns Hopkins scientists screened 175,000 small chemical compounds and identified a potent class of compounds that selectively slows down this protein's activity and, in a test tube, blocks TB growth, demonstrating that the protein is indeed a vulnerable target.

This class of chemical compounds attacks TB by inhibiting methionine aminopeptidase (MetAP), an essential enzyme found in organisms ranging from bacteria to humans, and that clearly has been conserved throughout evolution because of its important task of ensuring the proper manufacture of proteins.

"The MetAP inhibitors we discovered are hits, or leads in the sense that they provide a framework — a starting point — for the future development of an anti-TB drug," says Jun O. Liu, Ph.D., professor of pharmacology and molecular sciences, Johns Hopkins University School of Medicine.

The research appears in the January 29 edition of Chemistry & Biology.

The scientists cautioned that although the MetAP inhibitors prevent TB growth in test tubes, they have a long way to go before being declared safe and effective to treat TB patients. To understand how the MetAP inhibitors work, Liu suggests thinking of proteins as a strand of pearls folded in unique 3-D shapes, with each bead representing a protein building block, or amino acid. Invariably, the first bead, or amino acid, in every string, whether human or bacterial protein, is a methionine. The methionine ultimately needs to be removed in order for the protein to mature and fold correctly. Its removal is the job of enzymes called methionine aminopeptidases, or MetAPs.

"If you knock out this enzyme in TB bacteria, the bacteria will not survive," Liu says. "We expected that would happen, and confirmed it by manipulating how much enzyme is expressed to see what happens to the sensitivity of the bacteria when inhibitors are present."

What caught the team by surprise, however, was finding a potent class of compounds (called 2,3-dichloro-1, 4-naphthoquinone) that inhibits this enzyme. That discovery involved the use of large-scale, high-throughput screening of 175,000 compounds and measuring the potencies of a dozen related hits against the enzyme.

The final experiment by the team was to test the MetAP inhibitors on TB bacteria in culture to see if it had any effect on bacteria growth.

"Judging from potency, a MetAP inhibibitor alone probably won't wipe out TB," Liu says. "TB is so hard to treat that the standard therapy involves a cocktail of multiple drugs; no single compound is powerful enough. Our hope is that someday an inhibitor of MetAP will become a new component to enhance the existing therapy."

This study was funded by the National Institutes of Health.

In addition to Liu, authors of this paper are Omonike Olaleye, Tirumalai R. Raghunand, Shridhar Bhat, Sandeep Tyagi, Gyanu Lamichhane, Peihua Gu, Jiangbing Zhou, Ying Zhang, Jacques Grosset, and William R. Bishai, all of Johns Hopkins.

Maryalice Yakutchik | EurekAlert!
Further information:
http://www.jhmi.edu

Further reports about: MetAP MetAP inhibitors TB TB bacteria amino acid bacteria methionine aminopeptidase

More articles from Health and Medicine:

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>