Stage 6 mois : Synthèse d’analogues de nucléosides 3′,5′-biphosphates modifiés en position 2′ pour la détection d’ARN
RNA molecules perform various functional roles in biological processes such as transcription or epigenetic regulation of genes. Chemical modifications and labeling of RNA are of particular importance to study RNA in vitro, or investigate its interactions with proteins.1 Chemo-enzymatic synthesis enables the incorporation of modified nucleosides with diverse functional groups into RNA.2 This method involves preparing 3′,5′-biphosphate nucleosides, which are typically modified at the base or the 3′ position of the ribose. However, modification at the 2′-OH of these derivatives is less reported in the literature but allows diverse applications, including labeling, controlling RNA function, and probing folded structures.3
The objective of the internship is to develop a straightforward method for preparing 3’,5’-biphosphate cytidine (pCp) analogues modified at the 2’position by a reductive linker (Scheme 1). An approach on solid support developed in the laboratory will be considered, starting from a commercially available phosphoramidite.4 First, the impact of the chain length will be studied. Next, the methodology will be applied to the other nucleobases. These compounds will be tested as substrates for RNA T4 ligase (RNA synthesis and enzymatic reactions) and characterized by HPLC and MALDI-TOF mass spectrometry. These linkers bearing an alkyne group will be clicked onto magnetic beads allowing the recovery and detection of unmodified RNA under specific stimuli.
References: 1. Z. Cai et al. Nature, 2020, 582, 432. 2. Mattay, J. et al. Curr. Opin. Chem. Biol. 2021, 63, 46–56. 3. Merino, E. J. et al. J. Am. Chem. Soc. 2005, 127, 4223-4231. 4. Biscans, A. et al. Org. Biomol. Chem 2016, 14, 7010-7017.
| 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.
Contact: Dr. Christelle Dupouy,
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