Thesis presented October 20, 2016

Abstract:
DNA is an essential biomolecule, which ensures the support and the transfer of the genetic information in all organisms, and is involved in many interaction processes. The development of effective molecular tools interacting with DNA and highlighting this interaction is a field of research of high relevance, in order to understand essential biological events and for medical diagnostics. Thanks to their unique spectroscopic and magnetic properties, lanthanide ions (Ln³⁺) have proved to be very promising candidates in the design of such probes. In fact, luminescence of Tb³⁺ and Eu³⁺ is highly sensitive with narrow and specific emission bands, and is time-resolved with long luminescence lifetimes. Gd³⁺ ion, thanks to a high spin magnetic moment and a long electronic relaxation time, has interesting magnetic properties to enhance the nuclear paramagnetic relaxation of water protons. In this work, we take advantage of lanthanides’ properties within peptides, optimized for complexing these ions, and functionalized with a DNA binding unit. Developed Gd³⁺ complexes are powerful tools that can highlight the interaction with DNA, thanks to a significant increase of relaxivity at intermediate fields. This one is characteristic of the increase of the rotational correlation time inherent to the formation of the complex-DNA adduct. Moreover, the Tb³⁺ complexes include a sensitizer of this ion and a DNA binding unit, allowing the conception of effective DNA probes with optimized emission properties. A judicious choice of the trio “DNA binding unit – sensitizer – lanthanide” allows to switch off the lanthanide luminescence without DNA and to turn it on after interaction with this nucleic acid. These luminescent probes are also able to induce an increase of the metal-centered luminescence after interaction with other nucleic acids.

Keywords:
Peptide, Lanthanide, DNA, Probe, Luminescence, Relaxivity, DNA probe