Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists from the UJI use computational chemistry methods to know ...

09.05.2006
... about the nature of reactions in living beings and to be able to inhibit or accelerate them

Experimental methods have certain limits and there are times when nature briefly switches off the lights on scene to hide its tricks. One of these moments takes place during chemical reactions. All chemical reactions go through a sort of Limbo, a ghost-like stage between the initial reagents and the final product in which it is almost impossible to know experimentally what has occurred in the intermediate phase. A group of researchers from the Universitat Jaume I (UJI) of Castelló use techniques based on computational chemistry to theoretically model this unknown transition state and thus design compounds that either inhibit or enhance the action of biological catalysts.

A chemical reaction resembles the pass from one valley to another by way of a mountain. Valleys are stable areas, but if we attempt to go from one to the other, we need to cross an unstable point of maximum height along the way, that is, a hill. In the case of a chemical reaction, the initial and final molecules also have the features of stable structures that can be studied experimentally. To skip between them however, it is necessary to go through an unstable structure of maximum energy throughout the reaction, the hill of the chemical reaction, or in other words, its transition state.

This state is particularly interesting because biological catalysts or enzymes which accelerate chemical reactions taking place in living beings (from the transformation of food into energy to cell reproduction, among many others) do so by stabilising this unstable structure. Intervening in this transition state would allow us to stop or enhance a chemical reaction. However, this is so brief that it is impossible to know its structure in an experimental way. By means of theoretical simulations and the use of high-performance computers, researchers at the UJI have found out the way that certain chemical reactions follow, and have either suggested ways of blocking it, or proposed more efficient alternative routes.

“If we know the transition state structure, which is unstable by definition and, therefore, cannot be studied experimentally, we can then synthesise molecules that are similar to it yet chemically stable, which in other words is known as a transition state analogue”, explains Vicent Moliner, the person in charge of the research. The transition state analogue (TSA) is the molecular negative of the enzyme catalysing a certain reaction. This may then be used to block such enzyme action, by thus inhibiting an undesired chemical reaction from occurring.

“The development of this project is fundamental to improve the selectivity of drugs applied in chemical-therapeutic treatments. If we are able to know the structure of transition states in catalytic reactions involved, for example, in cell proliferation processes in tumours, we will be able to design drugs capable of stopping these reactions and preventing the spread of cancer”, explains Vicent Moliner. This principle can also be applied to other pathologies. “Among other systems, we are currently working with catechol-O-methyl transferase given its future applications in the treatment of degenerative diseases such as Parkinson’s disease. We are also working with HIV-1 IN, an enzyme that uses the HIV virus to replicate itself”, Moliner adds.

In the case of degenerative diseases, Moliner’s team has managed to define the structure of the transition state of a chemical reaction which is a key factor in the production of dopamine. The disequilibrium in the generation of this neurotransmitter is responsible for certain neurological diseases, such as Parkinson’s disease. “Knowing the structure of this reaction is a crucial step. We are now close to being able to suggest the synthesis of inhibitors that correct the disequilibrium of dopamine”, explains Vicent Moliner. The results have been published in several articles in the Journal of the American Chemical Society and in Chemical Society Reviews.

However, knowing the structure of chemical reactions is not only useful to block them, but also to propose biological catalysts for chemical reactions that we wish to accelerate. To this end, the TSA compound is introduced in a living system ( a rodent) to generate antibodies that will be macromolecules to complement TSA, that is, something like its photograph negative. Since antibodies are complementary to TSA, they can then be used as catalysts as they stabilise the transition state of the chemical reaction. These compounds are known as catalytic antibodies (CA).

“Nevertheless, catalytic antibodies that are generated so (germline CA) do not work very well as catalysts, so an improvement is sought for by means of selective mutations in the lab through trial and error tests (matured CA). However, this improvement is not very effective, and the work we have been carrying out in our group allows us to rationally determine what mutations should be tested in the lab to enhance the catalytic activity of CA”, Moliner points out. “These new molecules are particularly interesting in processes for which no catalyst exists to catalyse them, or for those processes in which the enzyme is not functioning properly”, Moliner indicates. These results have recently been published in the journal Angewandte Chemie.

Hugo Cerdà | alfa
Further information:
http://www.uji.es/ocit/noticies/detall&id_a=6308144

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>