Scientists From The UJI Use Computational Chemistry Methods To Know About The Nature Of Reactions In Living Beings And To Be Able To Inhibit Or Accele
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.
About UNIVERSITAT JAUME I
The Universitat Jaume I de Castelló is a higher education teaching and research institution created in 1991, which sets out to foster the social, economic and cultural development of the local community through the creation and diffusion of knowledge. From the outset, the Universitat Jaume I has worked towards the goal of establishing itself as a dinamic and entrepreneurial university, its aims being excellence in teaching, research and the services it provides for the community. It presently offers 26 degrees, all subject to continuous evaluation. It boasts some 13,000 students, a number which does not cause problems of overcrowding and enables it to offer personal student attention. This is also favoured by its setting, an attractive, modern, single site campus, which encourages closer social relationships, and which has excellent transport links to the city of Castelló and nearby towns. Quality in teaching The Universitat Jaume I teaches new, flexible and competitive programmes of study that enable students to face and satisfactorily meet every challenge set by modern society. The interdisciplinary nature of the courses at the Universitat Jaume I guarantees students'' autonomy and provides them with varied job opportunities. All programmes of study include work placements for all UJI students, which take place in companies and institutions. At the same time, in order to provide an all round education for everyone, educational exchanges with other countries are increasingly promoted. Competitive management Within the Spanish higher education system, the Universitat Jaume I stands out for its ability to obtain external resources for research and teacher development. Its commitment to service quality, social development and integral education of its members, whether scientific-technical or humanistic, are some of its defining characteristics, as well as the open and democratic management of the institution. Evolution and research, the keys to the future The Universitat Jaume I is a pioneer in the use of new information technologies for the diffusion of knowledge, based on the principle that communication and creativity are the most important tools for the future. The Universitat Jaume I was the first academic institution to be present in the World Wide Web (www) and to develop one of the most frequently used search engines in Spain (Dónde?). The Universitat Jaume I also plans to become the first university with a Centre for Education and New Technologies (CENT), with a direct connection to primary and secundary schools. The effort made in advancing scientific and technological innovation is complemented with a humanistic approach to education, a fact which favours students'' overall education as professionals and as members of society. At the same time, the Universitat Jaume I responds to social needs and demands with a diversified and flexible research offer, which emphasizes creativity, combines basic and applied research and supports emergent and interdisciplinary groups. . Degrees The Universitat Jaume I offers new, flexible and competitive programmes of study, which guarantee students'' professional and personal autonomy, and broaden their chances of succes in the labour market. Faculty of Humanities and Social Sciences BA in Advertising and Public Relations BA in English Philology BA in Humanities BA in Psychology BA in Psychopedagogy (2nd cycle only) BA in Translation and Interpreting Diploma in Early Childhood Education Diploma in Music Education Diploma in Physical Education Diploma in Primary Education Faculty of Law and Economics BA in Business Administration and Management BA in Law BA in Labour Sciences (2nd cycle only) Diploma in Business Studies Diploma in Labour Relations Diploma in Public Management and Administration Diploma in Tourism Higher School of Technology and Experimental Sciences Chemical Engineering Computer Science Engineering Industrial Engineering BSc in Chemistry Agricultural Technical Engineering: Horticulture and Gardening Speciality Industrial Technical Engineering: Mechanics Speciality Technical Engineering in Computer Management Technical Engineering in Computer Systems Technical Engineering in Industrial Design
UNIVERSITAT JAUME I
Campus Universitario Riu Sec
Avda.- Vicent Sos Baynat S/N
12006 Castellón De La Plana
http://www.uji.es/ocit/noticies/detall&id_a=6308144
Oamenii de ºtiinþã de la Uji Utilizaþi Computational Chemistry Metode sã ºtiu despre natura Reacþii În fiinþele vii ºi pentru a putea inhiba Sau Accele - Scientists From The UJI Use Computational Chemistry Methods To Know About The Nature Of Reactions In Living Beings And To Be Able To Inhibit Or Accele - articole medicale engleza - startsanatate