[The Svedberg seminar] – Targeting Non-Coding RNAs Using Synthetic Small Molecules: Original Targets for Innovative Therapies
September 25 @ 15:15 – 16:15 CEST
Dr Maria Duca
CNRS Research Director, Université Côte d’Azur, France
Website: icn.univ-cotedazur.fr/tna
Host: Duc Duy Vo duc.duy.vo@kemi.uu.se, UU
Bio
Dr. Maria Duca is head of Targeting of Nucleic Acids research group in the Institute of Chemistry of Nice (Université Côte d’Azur – CNRS). After undergraduate studies in Pharmacy and Medicinal Chemistry (Faculty of Pharmacy, University of Bologna, Italy), she obtained her PhD in Molecular Biochemistry under the supervision of Dr. Paola B. Arimondo (National Natural History Museum, Paris, France) working on topoisomerase II inhibitors. A 2-year post-doctoral training in Sydney Hecht’s lab (Department of Chemistry, University of Virginia, USA) allowed her to pursue the study of nucleic acids working on targeted protein mutagenesis. After CNRS recruitment as a Research Scientist in 2008 and promotion to Director of Research in 2022, her research activities focus on the targeting of non-coding RNAs using synthetic small molecules toward innovative therapeutic approaches for anticancer, antiviral and antimicrobial applications. She has been awarded the Michel Delalande award from the Académie de Pharmacie as well as national and international grants including H2020 grants. She is Associate Editor for RSC Medicinal Chemistry journal, chair of the Chemical Biology Initiative of EFMC as well as vice-president of the French medicinal chemistry society.
Targeting Non-Coding RNAs Using Synthetic Small Molecules: Original Targets for Innovative Therapies
RNA is one of the most intriguing and promising biological targets for the discovery of innovative drugs in a large number of pathologies and various biologically relevant RNAs that could serve as drug targets have already been identified.1 Among the most important ones, it is worth to mention prokaryotic ribosomal RNA which is the target of a number of currently employed antibiotics, viral RNAs such as TAR, RRE and DIS RNA of HIV-1 or oncogenic microRNAs that are tightly involved in the development and progression of various cancers.2 However, difficulties in the rational design of strong and specific small-molecule ligands renders this kind of molecules relatively rare.
In this presentation, the structure-based design of new RNA ligands targeting oncogenic RNAs will be illustrated together with the identification of new compounds bearing a promising biological activity.3 Also, it will be shown how the active binders can be employed as chemical tools for a better understanding of the formed interactions toward the design of optimized compounds.4 Finally, the use of RNA binders for the validation of new antibacterial targets against resistant bacterial strains will be described to highlight the potential of the small-molecule approach in RNA targeting.
References
[2] J. Falese, A. Donlic, A. Hargrove, Chem. Soc. Rev. 2021 50, 2224.
[3] D. D. Vo, C. Becquart, T. Tran, A. Di Giorgio, F. Darfeuille, C. Staedel, M. Duca, Org. Biomol. Chem. 2018 16, 6262; C. Staedel, T. Tran, J. Giraud, F. Darfeuille, A. Di Giorgio, N. Tourasse, F. Salin, P. Uriac, M. Duca, Sci. Rep. 2018 8, 1667.
[4] Maucort, C., Vo, D.D., Aouad, S., Charrat, C., Azoulay, S., Di Giorgio, A., Duca, M. ACS Med. Chem. Lett. 2021 12, 899; Tran, T.P.A., Poulet, S., Pernak, M., Rayar, A., Azoulay, S., Di Giorgio A., Duca, M. RSC Med. Chem. 2022 13, 311; Scheheoleva I., Fernandez-Remacha, D., Estrada-Tejedor, R., Duca, M., Michelet, V. Chem. Eur. J. 2023 doi.org/10.1002/chem.202300825
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