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
World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Information Technology
17.07.2018 | Materials Sciences
17.07.2018 | Power and Electrical Engineering