Objectif "Halogen bonding is an electron density donation-based weak interaction that has so far almost exclusively been investigated in computational and crystallographic studies. It shows high similaritiesto hydrogen bonding; however, its applicability for molecular recognition processes long remained unappreciated and has not been thoroughly explored.The main goals of this project are (1) to develop halogenated reporter compounds, using these (2) to perform the first ever systematic physicochemical study of halogen bonding in solutions, and (3) to apply the gained knowledge in structural biology through elucidation of the pharmacophore binding site of native proteins.Halogenated, paramagnetic, organometallic reporter compounds will be prepared using solution-phase organic synthesis. They will first be studied on small, well-designed organic model systems providing halogen bond donor and acceptor sites, mimicking those involved in the binding of pharmacophores to proteins and subsequently be used to investigate weak, protein-ligand interactions.The role of the participating halogen atom, the nature of the electron donors (N, O, S; n- and p-donors) and the influence of the environment (i.e. solvent) on the interaction, will be investigated. In this process NMR techniques will utilize paramagnetic effects and permit simultaneous characterization of bond strength and geometry of weak intermolecular complexes. It will be exploited to gain an atomic level understanding of anaesthesia with proteins involved in cellular calcium regulation. This in turn is of direct clinical relevance by providing a long-sought understanding of the disease malignant hyperthermia.In the proposed project I wish to combine my knowledge in chemistry, organometallic and physical chemistry to provide new theoretical insights in molecular recognition processes, to apply these for the understanding of pharmacophore–protein–Interaction and thereby give the basis for advances in drug developent." Champ scientifique natural scienceschemical sciencesinorganic chemistryorganometallic chemistrynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural scienceschemical sciencesinorganic chemistryhalogensnatural scienceschemical sciencesphysical chemistrynatural sciencesbiological sciencesmolecular biologystructural biology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2011-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Appel à propositions FP7-PEOPLE-2011-IEF Voir d’autres projets de cet appel Régime de financement MC-IEF - Intra-European Fellowships (IEF) Coordinateur GOETEBORGS UNIVERSITET Contribution de l’UE € 174 016,80 Adresse VASAPARKEN 405 30 Goeteborg Suède Voir sur la carte Région Södra Sverige Västsverige Västra Götalands län Type d’activité Higher or Secondary Education Establishments Contact administratif Annika Bergman (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
