Tonge will present these results at the American Society for Biochemistry and Molecular Biology's annual meeting in a talk titled "Slow Onset Inhibitors of Bacterial Fatty Acid Biosynthesis: Residence Time, In Vivo Activity and In Vivo Imaging." The talk will be held in Anaheim Convention Center Room 304C, on Sunday April 25 at 9:55 am PST.
"Our research team believes that many drugs are effective because they have long residence times on their target," says Tonge, Director of Infectious Disease Research at the Institute for Chemical Biology & Drug Discovery. "This concept has largely been ignored by investigators, and residence time is not usually incorporated into the drug discovery process."
Tonge explains that most drug discovery efforts obtain only data on the thermodynamic affinity of the drug for its target, measurements that are made at constant drug concentration. However, the Stony Brook University-led research factors in residence time, which he emphasizes is critical for activity in vivo where drug concentrations fluctuate with time.
"The central component of our work is that the length of time a drug remains bound to a target is very important for the activity of the compound in vivo," he adds.
Tonge, together with collaborators at Colorado State University and the University of Würzburg in Germany, have developed a series of compounds that inhibit an enzyme target from Francisella tularensis, where the in vivo antibacterial activity of the compounds correlates with their residence time on the target and not with their thermodynamic affinity for the target. This resulted in a direct correlation between residence time and in vivo activity against an infectious agent.
The research team has also developed a long residence time inhibitor of an enzyme drug target in Mycobacterium tuberculosis and demonstrated that this compound has antibacterial activity in an animal model of tuberculosis.
Because compounds with long residence times should accumulate in bacteria, Tonge explains that the research may lead to the development of agents to image bacterial populations in vivo using positron emission tomography. He says that researchers could then further the concept and develop a method for non-invasive imaging of bacterial populations in humans for both diagnostic purposes and also to monitor bacterial load during drug therapy, thereby helping to chart a drug's effectiveness against bacterial infection.
Nicole Kresge | EurekAlert!
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences