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

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Epoxy compound gets a graphene bump

14.11.2018 | Materials Sciences

Microgel powder fights infection and helps wounds heal

14.11.2018 | Health and Medicine

How algae and carbon fibers could sustainably reduce the athmospheric carbon dioxide concentration

14.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>