Spectrometry Applied to Structural Characterization team (SACS)

Mass spectrometry (MS) and nuclear magnetic resonance (NMR) are orthogonal techniques that can be combined to obtain complementary information for best characterization of unknown or complex samples. In our research team, this approach is implemented:

• To characterize dendrimer/ligand complexes by combining liquid state NMR, tandem mass spectrometry and ion mobility spectrometry;
• To better understand the MALDI process by studying, in solid state NMR, structuration of samples to be subjected to laser irradiation.

Skills:

HPLC, HPLC/Fl, HPLC/MS

Synthesis of molecules targeting the metabolism of cancer cells

For more than 25 years, our team has been interested in spin trapping and has significantly contributed to the discovery of some of the best families of spin traps. A better understanding of the trapping process and improvements in spin trap design has so become possible. Special attention has been devoted to improving (i) the life time of adducts issued from the trapping of the superoxide radical anion, (ii) the kinetics of superoxide radical trapping, (iii) the biodistribution of spin traps in biological systems, and (iv) the protection of spin adducts in the presence of biological reducing agents. Recently, a new approach has been developed to protect spin adducts toward bioreductants by grafting spin traps inside mesoporous silica.

We also work on fluorescent probes based on hydroethidine (HE). We have contibuted to a better understanding of the kinetics and of the mechanism of reaction of superoxide with HE, and improved probes could be developed. Our efforts also focused on structure activity relationships concerning HE in this context and ongoing efforts are devoted to better control the probe biodistribution.

Our activity in the frame of free radical detection has lead us to concentrate on processes involved in mitochondria which is one of the main sources of superoxide. The design and preparation of biological agents targeting mitochondria and the metabolism of cancer cells is another of our areas of interest. To efficiently target mitochondria, triphenylphosphonium (TPP) is one of the most relevant vectors enabling the accumulation of compounds with a biological activity in mitochondria. We currently work on improving designs, preparing and testing in biological systems mitochondria-targeting molecules such as nitroxides, nitrones, contrast agents, mitochondria inhibitors and anticancer agents. These last years, we got excellent results with derivatives of metformin, honokiol or lonidamine to limit the proliferation of cancer cells from pancreas, lung or brain.