Patients who suffer from gingivitis are often advised to use disinfectant mouthwashes. In the future, the active ingredients in these products could be used in a completely different area: As scientists have reported in the journal Angewandte Chemie, Chlorhexidin and Alexidin increase programmed cell death and may be effective against cancers of the mouth and throat.
Sometimes researchers discover that established drugs have other effects in addition to those for which they were actually approved. For example acetylsalicylic acid (Aspirin) has commonly been used to treat pain and fever; more recently, however, it has also been prescribed to thrombosis-prone patients as a blood thinner.
A team headed by Thorsten Berg is now convinced that many low-molecular drugs already in use demonstrate previously unrecognized activity toward interactions between proteins, which may be of therapeutic use.
The team of scientists from the University of Leipzig, the Max Planck Institute for Biochemistry, the Center for Integrated Protein Science Munich, the Helmholtz Center Munich, the Technical University Munich, and the ETH Zurich were out to use a protein–protein interaction relevant for human health to demonstrate the interactions between two proteins whose interaction controls apoptosis, or programmed cell death. Both proteins are from the same protein family. The first protein, Bad, initiates apoptosis-promoting protein to inhibit it.
The researchers proceeded to screen a collection of over 4000 substances known as a compound library. The majority of the compounds in the library are small molecules in clinical use. Binding experiments were used to determine which of the substances inhibit the binding of the two target proteins. To determine the specificity of the "hits", their effects on other protein–protein interactions were also tested.
Berg and his co-workers were successful: Chlorhexidin, the active component in commercial oral disinfectants such as Chlorhexamed, Chlorhexal, Periogard, Corsodyl, and Chlorohex; as well as Alexidin, the active component in Esemdent, both inhibit the binding of the apoptosis inhibitor to the apoptosis trigger. Chlorhexidin's effect is specific, while Alexidin has additional very weak effects on other proteins.
Why are apoptosis proteins interesting? Apoptosis is decreased in tumor cells, so the cells do not die off and continue to divide. One reason for this is that they produce too much of the apoptosis-inhibiting protein. In experiments with cultures of cells from various tongue and throat carcinomas, both compounds caused increased apoptosis. This effect is much stronger in the cancer cells than in healthy cells. It may be possible to use these drugs in therapeutic applications.
The researchers hope to find other protein-protein interactions that could be targeted with approved small-molecule drugs.About the Author
Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/10.1002/anie.201208889
27.03.2015 | Oak Ridge National Laboratory
How did the chicken cross the sea?
27.03.2015 | Michigan State University
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
27.03.2015 | Agricultural and Forestry Science
27.03.2015 | Materials Sciences
27.03.2015 | Ecology, The Environment and Conservation