Conception d'inhibiteurs d'interactions protéine-protéine : Application à l'assemblage des nucléosomes – BREAKABOND

Over the past few years inhibition of protein-protein interactions by synthetic compounds has emerged as an exciting and realistic technology to interfere with regulatory processes in living organisms. We propose an innovative strategy to design potent inhibitors of macromolecular interactions. The main idea is to increase the affinity and the specificity of designed molecules by combining binding epitopes of one targeted protein. This strategy will be validated on Asf1, a histone chaperone essential for the early steps of the chromatin assembly process. Involved in a dense network of interactions, Asf1 is crucial for replication, cellular responses to DNA damage and maintenance of epigenetic information. We expect that impeding chromatin assembly during cell proliferation or after DNA damage repair will be deleterious to the cell physiology and thus will pave the way for the design of novel anticancer strategies. ...