q&more
My watch list
my.chemie.de  
Login  

News

A Step Ahead in Pharmaceutical Research

Researchers have developed a method that makes it possible to measure the activation of receptors in a very short time

Hannes Schihada

Novel sensors make it possible to measure the activation or deactivation of GPCRs with high-throughput methods.

07-Sep-2018: Hormones and other neurotransmitters, but also drugs, act upon receptors. “Their active substances bind to the receptors and modify the three-dimensional receptor arrangement regulating the downstream signal pathways,” says Hannes Schihada from the Institute for Pharmacology and Toxicology at the University of Würzburg (JMU).

A special case are G protein–coupled receptors (GPCR). “About 30 percent of all authorized drugs worldwide act upon these receptors,” explains Hannes Schihada, “but their potential is not yet fully utilized.” So far, it was not possible to test the effect of millions of potential drugs on the GPCR arrangement within a very short time. “This has been a stumbling block to the discovery of novel pharmaceutical substances and the research of still unknown GPCRs,” says Dr. Isabella Maiellaro, who is in charge of the project together with Professor Martin Lohse.

The JMU team has now developed a method that allows the determination of both activity and potency of GPCR ligands in living cells using high throughput technology.

What the new method can do

The name of the method is BRET (bioluminescence resonance energy transfer-based sensor design). “It can be used not only for GPCRs but for a lot of different biomolecules,” explains Schihada.

The universal sensor design now allows the exploration of receptor conformational changes in living cells with the high-throughput method. This enables a much faster pharmacological characterization by a high number of test combounds that directly act on the receptor, independently of their downstream receptor signal pathways.

“This technology can contribute to a faster and better understanding of the different levels of effectiveness of drugs and thus drive the development of novel therapeutic concepts,” says Schihada. The study of novel receptor targets will yield a higher array to develop drugs that have less side-effects and are more efficient.

Furthermore, the sensors could help to better understand what is called orphan GPCRs – GPCRs whose function and ligands are still largely unknown. “With these findings we can lay the foundation for the treatment of severe diseases that were hitherto difficult to treat, such as Alzheimer’s or multiple sclerosis,” says the scientist.

The research has been funded by the Federal Ministry for Education and Research. The scientists now want to expand their range of sensors suitable for high throughput.

Original publication:
Hannes Schihada, Sylvie Vandenabeele, Ulrike Zabel, Monika Frank, Martin J. Lohse & Isabella Maiellaro; "A universal bioluminescence resonance energy transfer sensor design enables high-sensitivity screening of GPCR activation dynamics"; Nature Communications Biology; 2018

Facts, background information, dossiers

  • drug discovery
  • receptors
  • G protein-coupled receptors
  • biomolecules
  • high-throughput mea…

More about Uni Würzburg

  • News

    Inert Nitrogen Forced to React with Itself

    Direct coupling of two molecules of nitrogen: chemists from Würzburg and Frankfurt have achieved what was thought to be impossible. This new reaction is reported in Science magazine and opens new possibilities for one of the most inert molecules on earth. Constituting over 78 % of the air ... more

    Protein BRCA1 as a Stress Coach

    Two proteins work hand in hand to ensure that the tumour cells of neuroblastoma can grow at full speed. In "Nature", a Würzburg research team shows how the proteins can do this. Anyone who has ever studied the molecular basis of breast cancer will probably have heard of the abbreviation BR ... more

    New findings about anti-malaria drug

    Artemisinin is derived from the leaves and flowers of the annual mugwort (Artemisia annua) and has been used in traditional Chinese medicine for centuries. The effectiveness was investigated by the Chinese researcher Tu Youyou. Her research was 2015 rewarded with the Nobel Prize. Artemisini ... more

  • q&more articles

    High-tech in the beehive

    Healthy honeybee colonies are crucial to maintaining the natural diversity of flowering plants and the global production of plant-derived foodstuffs. As much as 35 % of this production depends on insect-based pollination, in which the honeybee (Apis mellifera) plays a leading role. For fund ... more

  • Authors

    Prof. Dr. Jürgen Tautz

    studied biology, geography and physics at the University of Konstanz before receiving his doctorate from the University on an ecology-related subject. Work in insect, fish and frog bio-acoustics was followed by his foundation of the BEEgroup at the University of Würzburg in 1994, a group th ... more

  • Videos

    High-tech in the beehive

    more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by:

 

Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE