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Home NEWS Science News Chemistry

Pharmaconutrition — Modern drug design for functional studies

Bioengineer by Bioengineer
July 1, 2019
in Chemistry
Reading Time: 5 mins read
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Bitter (taste) receptor with health effect?

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Credit: Dr. Antonella Di Pizio / Leibniz-LSB@TUM

Antonella Di Pizio and Maik Behrens of the Leibniz-Institute for Food Systems Biology at the Technical University of Munich, together with their cooperation partners, have developed highly effective activators for the bitter receptor TAS2R14 in a German-Israeli research project. The new substances are used to investigate the as yet unknown physiological functions of the receptor, for example, in the human immune system.

The team of scientists published their results in the journal Cellular and Molecular Life Sciences (Di Pizio et al., 2019; DOI: 10.1007/s00018-019-03194-2).

Bitter (taste) receptor with health effect?

It has only been known for approximately 15 years that humans detect bitterness with the aid of 25 different receptor variants. TAS2R14 is one of these. However, unlike most of the other bitter receptors, it detects a broad spectrum of bitter substances. In addition to secondary plant substances, such as caffeine, its activators also include medications. However, the bitter receptor is not just relevant for taste perception. Recent findings indicate that it provides other physiological functions that are important for our health. It is found on lung and testicle cells and plays a role in the innate immune response.

Old drug substance as the basis for modern drug design

In order to specifically investigate the manifold functions of TAS2R14 in different organs and tissues, among other things, highly effective (potent) activators of the receptor are necessary. Using a structure-based computer-aided modeling approach, the German-Israeli team of scientists has now succeeded for the first time in synthesizing three such highly potent substances. The original substance for the drug design was the drug flufenamic acid. The well-known active ingredient is one of the non-steroidal anti-inflammatory drugs and is contained in muscle and joint salves. It has an anti-inflammatory and analgesic effect, in that it blocks enzymes that promote the release of prostaglandins.

“We chose this active ingredient as the basis for our investigations because it stimulates the receptor even in the most minute concentrations. This means that approximately eight millionths of a gram of the substance per liter are already sufficient for this purpose,” explains bioinformatician and lead author, Antonella Di Pizio. The new derivatives are extremely potent activators, more effective than the known drug, and in the future they will be used as tools in functional studies.

A new research area “pharmaconutrition” with a systems biology approach

“Due to the many new findings, we no longer regard bitter substances exclusively as pure flavoring components, but also as medically effective nutritional components,” says molecular biologist Maik Behrens. “Likewise, today bitter receptors must no longer be viewed as just sensors that warn us of potentially toxic substances before swallowing.” To research the correlations between bitter substances, bitter receptors and the human organism a new, far-reaching systems biology approach is required, the biologist continued. The Leibniz Institute is pursuing this approach by combining basic molecular research with the latest methods of bioinformatics and high-throughput technologies.

###

Original Publication:

Di Pizio A, Waterloo LAW, Brox R, Löber S, Weikert D, Behrens M, Gmeiner P, Niv MY (2019) Cellular and Molecular Life Sciences, DOI: 10.1007/s00018-019-03194-2. Rational design of agonists for bitter taste receptor TAS2R14: from modeling to bench and back

Background Information:

Not just good for smelling and tasting-Chemoreceptors offer approaches for the development of new drug therapies

Odor and taste receptors are found not only in the nose and mouth. Recent studies indicate that they perform other functions in the body, for example, in the immune system or the regulation of metabolism. Therefore, they could serve as starting points for computer-assisted development of new therapeutics. A review article of the Leibniz-LSB@TUM now summarizes the current data situation on this topic.

Di Pizio A, Behrens M, Krautwurst D. (2019) International Journal of Molecular Sciences, DOI: 10.3390/ijms20061402. Beyond the flavor: the potential druggability of chemosensory GPCRs

Read also:

Reengineering the ligand sensitivity of the broadly tuned human bitter taste receptor TAS2R14. Nowak S, Di Pizio A, Levit A, Niv MY, Meyerhof W, Behrens M. Biochim Biophys Acta. 2018 Jul 12. pii: S0304-4165(18)30200-9. https://www.sciencedirect.com/science/article/pii/S0304416518302009; https://doi.org/10.1016/j.bbagen.2018.07.009

Probing the binding pocket of the broadly tuned human bitter taste receptor TAS2R14 by chemical modification of cognate
agonists. Karaman R, Nowak S, Di Pizio A, Kitaneh H, Abu-Jaish A, Meyerhof W, Niv MY, Behrens M. Chem Biol Drug Des. 2016 Jul; 88(1):66-75. doi: 10.1111/cbdd.12734.

The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14. Levit A, Nowak S, Peters M, Wiener A, Meyerhof W, Behrens M, Niv MY. FASEB J. 2014 Mar; 28(3):1181-97. doi: 10.1096/fj.13-242594.

Contact:

Dr. habil. Maik Behrens

Section II, Work Group Taste Systems Reception & Biosignals

Leibniz-Institute for Food Systems Biology at the TU Munich (Leibniz-LSB@TUM)

phone: +49 816171 2987

e-mail: [email protected]

Profile of Dr. habil. Maik Behrens: https://www.leibniz-lsb.de/institut/mitarbeiterinnen/kurzprofil-dr-habil-maik-behrens/

Dr. Antonella Di Pizio

Section III, Work Group Computational Pharmacology

Leibniz-LSB@TUM

phone: +49 816171 2904

e-mail: [email protected]

Profile of Dr. Antonella Di Pizio: https://www.leibniz-lsb.de/institut/mitarbeiterinnen/kurzprofil-dr-antonella-di-pizio/

Press Contact:

Dr. Gisela Olias

Press and Public Relations

Leibniz-LSB@TUM

phone: +49 816171 2980

e-mail: [email protected]

http://www.leibniz-lsb.de

The Leibniz-Institute for Food Systems Biology at the Technical University of Munich (Leibniz-LSB@TUM) has a unique research profile. Its researchers combine methods of basic biomolecular research with analytical methods of bioinformatics and analytical high-performance technologies. Their goal is to decode the complex ingredient profiles from raw materials to the final food products and to elucidate their function as biological active molecules on humans. Based on their studies, the scientists develop products, which are as healthy as they are tasty. These foods will help to provide a sustainable and sufficient stream of food for future generations. In addition, the new scientific findings will be used to develop personalized nutritional concepts that, for example, help people with food intolerance without compromising quality of life and endangering their health.

The Leibniz LSB@TUM is a member of the Leibniz Association, which connects 95 independent research institutions. Their orientation ranges from the natural sciences, engineering and environmental sciences through economics, spatial and social sciences to the humanities. Leibniz Institutes devote themselves to social, economic and ecological issues. They conduct knowledge-oriented and application-oriented research, also in the overlapping Leibniz research networks, are or maintain scientific infrastructures and offer research-based services. The Leibniz Association focuses on knowledge transfer, especially with the Leibniz Research Museums. It advises and informs politics, science, business and the public. Leibniz institutions maintain close cooperation with universities – among others, in the form of the Leibniz Science Campuses, industry and other partners in Germany and abroad. They are subject to a transparent and independent review process. Due to their national significance, the federal government and the federal states jointly fund the institutes of the Leibniz Association. The Leibniz Institutes employ around 20,000 people, including 10,000 scientists. The entire budget of all the institutes is more than 1.9 billion euros.

Media Contact
Dr. Gisela Olias
[email protected]

Original Source

https://www.leibniz-lsb.de/en/press-public-relations/pressemitteilungen/pm-20190701-pressemitteilung-pharmakonutrition/

Related Journal Article

http://dx.doi.org/10.1007/s00018-019-03194-2

Tags: BiochemistryBioinformaticsBiologyBiomedical/Environmental/Chemical EngineeringMedicine/HealthMolecular BiologyNutrition/NutrientsPharmaceutical SciencesPhysiology
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