Objectif The aim of my project is to establish a multidisciplinary platform for quantitative biophysical analysis of protein-protein interactions in health and disease as a basis for drug design: (1) Analyzing protein-protein interactions at the molecular level in healthy systems; (2) Understanding what goes wrong in disease at the molecular level; (3) Development of drugs that will restore the biological system to its healthy conditions. My team will apply this approach to establish the concept of shifting the oligomerization equilibrium of proteins as a therapeutic strategy. I will expand the concepts of allosteric inhibitors and chemical chaperones, and develop the “shiftides”: peptides that shift the oligomerization equilibrium of a protein to modulate its activity, as a new and widely applicable methodology for drug design. I will apply this concept for: (1) inhibiting a protein by binding preferentially to the inactive oligomeric state and shifting the oligomerization equilibrium of the protein towards it; I have demonstrated the feasibility of this approach and developed promising anti-HIV peptides that inhibit the HIV-1 integrase and consequently HIV-1 replication in cells by shifting the integrase oligomerization equilibrium from the active dimer to the inactive tetramer. My team will further develop these peptides, and apply the same approach to inhibit the HIV proteins reverse transcriptase and protease; (2) Activating a protein by binding preferentially to the active oligomeric state and shifting the oligomerization equilibrium towards it: This will be applied for activation of the tumor suppressor p53, by shifting its oligomerization equilibrium from the inactive dimer to the active tetramer. Such shiftides will serve as anti-cancer lead compounds. My project will open new doors in the field of drug design, and at the end of the five-year period will result in a general new methodology to affect protein function for medical purposes. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesbasic medicinemedicinal chemistrymedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIV Mots‑clés AIDS biophysics cancer drug design oligomerization protein Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-PE4 - ERC Starting Grant - Physical and Analytical Chemical sciences Appel à propositions ERC-2007-StG Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil THE HEBREW UNIVERSITY OF JERUSALEM Contribution de l’UE € 1 250 000,00 Adresse EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Israël Voir sur la carte Type d’activité Higher or Secondary Education Establishments Chercheur principal Assaf Friedler (Dr.) Contact administratif Eran Vardi (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire THE HEBREW UNIVERSITY OF JERUSALEM Israël Contribution de l’UE € 1 250 000,00 Adresse EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Voir sur la carte Type d’activité Higher or Secondary Education Establishments Chercheur principal Assaf Friedler (Dr.) Contact administratif Eran Vardi (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée