Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Successful combination: virtual screening and cell culture research-Interferon inhibitor discovered

17.11.2011
Interferon alpha plays a central role in severe autoimmune disorders.

Inhibitors are not available to date. In collaboration with researchers of the ETH Zurich, Switzerland, scientists at the Paul-Ehrlich-Institut have now succeeded in identifying a substance that inhibits interferon alpha release. Their innovative research approach may not only be of significance for the search of an active substance as such but also for the rapid identification of inhibitors of important protein-protein interactions. The journal "Angewandte Chemie" (Applied Chemistry) reports on the research results as an 'epub ahead of print'(Hot Paper; DOI: 10.1002/anie.201105901)

Type I interferons, such as interferon alpha, form part of the innate immune system. Humans would not be viable without them. However, there is a downside to these important messenger substances of our immune system. Thus, constantly elevated interferon alpha levels may cause chronic inflammatory reactions contributing to autoimmune disorders such as Lupus erythematodes. So far, no active substance is available which is able to inhibit interferon release and its effects in a targeted manner. Researchers from a variety of fields of knowledge have united in search of an active substance that inhibits the interaction between the interferon receptor, which is the same for all type I interferons, and interferon alpha:

Scientists of the Institute of Pharmaceutical Sciences of the Eidgenössische Technische Hochschule (ETH, Federal Institute of Technology) at Zurich, Switzerland, the head of which is Professor Gisbert Schneider, and immunologists of the Paul-Ehrlich-Institut under the supervision of PD Dr Zoe Waibler, head of one of the temporary research groups of the institute. Dr Schneider and his co-workers screened more than 500,000 substances for their potential ability to bind to a surface area of interferon alpha with the aid of several computer-assisted methods. These methods were used to predict the said surface area as important for the interaction with the receptor.

To identify suitable substances, these 3D conformational studies were performed partly with the aid of innovative software methods developed at the ETH at Zurich: "Innovative approaches to computer-aided protein structure analyses have provided us with crucial hints where and how we should search. This study emphasises the tremendous potential of transdisciplinary concepts for active substance research", sayid Schneider.

The six most promising candidate substances were selected and Dr Waibler and her co-workers used them in cell culture assays. For this purpose, the PEI researches used plasmacytoid dendritic cells – the main producers of interferon alpha, which they harvest from bone marrow. Waibler and colleagues had already proved in previous research projects that adding the modified vaccine virus Ankara (MVA) leads to a pronounced interferon alpha response. MVA is a strongly attenuated and thus innocuous pox virus. Two of the six test substances had to be eliminated, due to their insufficient solubility. Among the four remaining ones, however, one of them was a direct hit for the investigators: While the three other substances showed no effects, one of these low molecular chemical compounds efficiently inhibited the production of interferon alpha. "We were ourselves surprised at the incredibly good results obtained from the combination of our two methods", reports Dr Waibler. In other experiments, the PEI investigators proved that the new substance was also able to inhibit interferon alpha release to other danger signals such as other viruses or double-stranded DNA. On the other hand, however, they also identified that at high concentrations of the active substance, a cell-toxic effect developed. The next step therefore is to derive other candidate substances from the leading substance thus discovered, which inhibit receptor binding of interferon selectively and still more specifically, and at the same time, show no toxicity even in high concentrations.

Apart from the concrete search of a new interferon alpha inhibitor, the methodological approach of the two investigators may be of importance. Thanks to the innovative combination of these very differing technologies, many more substances may be found in a short period of time which may be able to inhibit particular protein-protein interactions.

Dr. Susanne Stöcker | idw
Further information:
http://www.pei.de/
http://onlinelibrary.wiley.com/doi/10.1002/anie.201105901/abstract

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>