Stage 5-6 mois : Synthèse d’oligonucléotides fluorés pour des applications thérapeutiques de type miARN.
Master 2 or Engineer student Internship (5-6 months) from January/February 2026
Synthesis of fluorinated oligonucleotides for miRNA therapeutic applications
Nucleic acid-based therapeutics such as micro-RNA (miRNA), small interfering RNA (siRNA) and more recently messenger RNA (mRNA) vaccine have emerged and represent today, key tools in a wide range of diseases. Since natural oligonucleotides (ONs) are rapidly metabolized in biological media by nucleases and suffer from a poor cellular uptake, several chemical modifications were envisaged and led to the conception of ONs analogs with improved biological properties1. Our project deals with the design and synthesis of new ON series that would be able to counteract the main limitations of current therapeutic ONs. In front of the importance of the fluorine atom in medicinal chemistry,2 we will be particularly interested in the preparation of fluorinated nucleic acids that have been less explored nowadays.3
Based on preliminary results, the objective of the internship is to synthesize RNAs modified at the 2′ position with fluorinated groups 4. Various phosphoramidites supplied by the LCMT team (Univ. Caen) will be incorporated into ONs on solid support (RNA Synthesis) (Scheme 1). These ONs will be purified by HPLC and characterized by MALDI-TOF Mass Spectroscopy. The physicochemical properties (circular dichroism and melting temperature experiments) and enzymatical stabilities of these modified duplexes will then be determined. The best candidates will be tested by biologist collaborators (Biotargen team, Univ. Caen) in validated models of miRNA approaches to evaluate their biological effectiveness.
References:
1. W. B. Wan, P. P. Seth, J. Med. Chem. 2016, 59, 9645-9667. 2. E. P. Gillis, K. J. Eastman, M. D. Hill, D. J. Donnelly, N. A. Meanwell, J. Med. Chem. 2015, 58, 8315-8359. 3. F. Guo, Q. Li, C. Zhou, Org. Biomol. Chem. 2017, 15, 9552-9565. 4. E. Pfund, C. Dupouy, S. Rouanet, R. Legay, C. Lebargy, J. J. Vasseur, T. Lequeux, Org. Lett. 2019, 21, 4803-4807.
Location:IBMM, University of Montpellier, France Team ChemBioNAC: https://chembionac.com/
Profile of the candidate:Master 2 or Engineer student with excellent background in organic chemistry and a strong interest in nucleic acids chemistry. Please provide CV, cover letter and copy of the grades from previous years.
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