Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New discovery solves problem of anti-inflammatory substance

04.03.2014

There have been great expectations regarding the production of a drug to block the enzyme LTA4 hydrolase, which plays a key role in the body's inflammatory response.

However, in clinical trials, such molecules have proven to be only moderately effective. Now, researchers at Karolinska Institutet have successfully refined their understanding of why previous substances have been less effective – and in so doing have produced a molecule that gets around the problem. Consequently, there is once again hope of a new anti-inflammatory drug based on the principal of blocking LTA4 hydrolase, which could provide relief in diseases such as COPD, the vascular disease arteriosclerosis and chronic eczema.

Dr. Jesper Z. Haeggström, Karolinska Institutet

Jesper Z. Haeggström is a Professor of Molecular Eicosanoid Research at Karolinska Institutet in Stockholm, Sweden.

Credit: Karolinska Institutet

The enzyme LTA4 hydrolase has two functions. One is to produce LTB4, which contributes to the inflammatory reaction. The other is to inactivate the tripeptide Pro-Gly-Pro, which is formed during degradation of connective tissue and which also contributes to inflammation. In the first pathway, the enzyme LTA4 hydrolase evokes an inflammatory process, while it contributes to healing in the second.

"It could be considered remarkable that the same enzyme has two activities that are completely opposite. But this is more understandable if you look at it over time: in the first stage, the enzyme creates inflammation at the site of an injury, thus attracting white blood cells, and in the second stage it contributes to healing by inhibiting the inflammation," says Jesper Z. Haeggström, Professor of Molecular Eicosanoid Research in the Department of Medical Biochemistry and Biophysics at Karolinska Institutet.

Previous attempts to produce an anti-inflammatory drug that blocks LTA4 hydrolase have knocked out both of these functions. This is probably why the effects have so far been only moderate. Using x-ray crystallography to study LTA4 hydrolase, Jesper Z. Haeggström and his colleagues have been able to demonstrate that the formation of LTB4, which contributes to the inflammatory process and the inactivation of Pro-Gly-Pro, takes place at different parts of the enzyme's active site – the part of the enzyme used for biochemical communication.

They have used this information to produce a molecule that inhibits LTA4 hydrolase from producing LTB4, while the inactivation of Pro-Gly-Pro is maintained. This means that LTA4 hydrolase acts as an anti-inflammatory in both pathways; awakening new hopes of producing a drug that acts on this enzyme.

In the long-term, the researchers believe that a drug based on their molecule could be used to treat COPD (chronic obstructive pulmonary disease), arteriosclerosis and various types of inflammatory skin disease such as chronic eczema. The study has been financed by the Swedish Research Council, the EU, VINNOVA, Stockholm County Council and Dr. Hans Kröner Graduiertenkolleg.

###

Publication: 'Binding of Pro-Gly-Pro at the active site of leukotriene A4 hydrolase and development of an epoxide hydrolase selective inhibitor', Alena Stsiapanava, Ulrika Olsson, Min Wan, Thea Kleinschmidt, Dorothea Rutishauser, Roman Zubarev, Bengt Samuelsson, Agnes Rinaldo-Matthis and Jesper Z. Haeggström, PNAS, online early edition 3-7 March 2014.

Karolinska Institutet - a medical university: ki.se/english

Press Office | EurekAlert!

Further reports about: COPD LTB4 activities anti-inflammatory arteriosclerosis eczema enzyme healing hydrolase inflammation inflammatory skin

More articles from Life Sciences:

nachricht Discovery of an unexpected function of a protein linked to neurodegenerative diseases
28.04.2015 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Rubber from dandelions / Scientists identify key components in the formation of rubber
28.04.2015 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fast and Accurate 3-D Imaging Technique to Track Optically-Trapped Particles

KAIST researchers published an article on the development of a novel technique to precisely track the 3-D positions of optically-trapped particles having complicated geometry in high speed in the April 2015 issue of Optica.

Daejeon, Republic of Korea, April 23, 2015--Optical tweezers have been used as an invaluable tool for exerting micro-scale force on microscopic particles and...

Im Focus: NOAA, Tulane identify second possible specimen of 'pocket shark' ever found

Pocket sharks are among the world's rarest finds

A very small and rare species of shark is swimming its way through scientific literature. But don't worry, the chances of this inches-long vertebrate biting...

Im Focus: Drexel materials scientists putting a new spin on computing memory

Ever since computers have been small enough to be fixtures on desks and laps, their central processing has functioned something like an atomic Etch A Sketch, with electromagnetic fields pushing data bits into place to encode data.

Unfortunately, the same drawbacks and perils of the mechanical sketch board have been just as pervasive in computing: making a change often requires starting...

Im Focus: Exploding stars help to understand thunderclouds on Earth

How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was discovered, more or less by coincidence, that cosmic rays provide suitable probes to measure electric fields within thunderclouds. This surprising finding is published in Physical Review Letters on April 24th. The measurements were performed with the LOFAR radio telescope located in the Netherlands.

How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was...

Im Focus: On the trail of a trace gas

Max Planck researcher Buhalqem Mamtimin determines how much nitrogen oxide is released into the atmosphere from agriculturally used oases.

In order to make statements about current and future air pollution, scientists use models which simulate the Earth’s atmosphere. A lot of information such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

HHL Energy Conference on May 11/12, 2015: Students Discuss about Decentralized Energy

23.04.2015 | Event News

“Developing our cities, preserving our planet”: Nobel Laureates gather for the first time in Asia

23.04.2015 | Event News

HHL's Entrepreneurship Conference on FinTech

13.04.2015 | Event News

 
Latest News

Rapid Detection of Cracks and Corrosion using Magnetic Stray Flux

28.04.2015 | Innovative Products

Discovery of an unexpected function of a protein linked to neurodegenerative diseases

28.04.2015 | Life Sciences

Rubber from dandelions / Scientists identify key components in the formation of rubber

28.04.2015 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>