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.
"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!
Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications
Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
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...
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...
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...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine