Selective recognition of threeway DNA junctions with designed peptidomimetics

Abstract

Non-canonical DNA structures, such as three-way DNA junctions (3WJs), formed during DNA replication, have emerged as promising alternative DNA targets for the development of new drugs with attractive therapeutic properties. In this context, supramolecular helicates have shown high selectivity and binding affinity for 3WJs, but their use in this field is hampered by the lack of synthetic versatility and a general strategy to their enantioselective synthesis. In this thesis, we describe the stereoselective self-assembly of helicates derived from peptide ligands equipped with 2,2’-bipyridine coordinating residues, as well as the implementation of a new strategy that relies on the cooperative 3WJ-binding mechanism of natural proteins, to yield new systems with selective 3WJs recognition properties.