PhD student (M/F) in Molecular Chemistry

Job Description

Thesis Subject

Bioinspired synthesis of C-glycoconjugates by remodeling of the catalytic pocket of glycosidases
Description of the project: Galactofuranose (Galf) is one of the most abundant hexofuranoses identified to date and has been found in the glycocalyx of certain microorganisms, often pathogens such as Leishmania, Trypanosoma or Mycobacteria1,2. As the Galf scaffold is completely xenobiotic in mammals, it is an attractive target for new pharmacophore. Already, different families of alkyl O- and S-galactofuranosides have demonstrated growth inhibition against strains of Mycobacteria or Leishmania with micromolar minimum inhibitory concentration3,4. However, their therapeutic use is limited by high sensitivity to enzymatic or acidic hydrolysis. Replacing the O-glycosidic bond with a C-glycosidic bond not only improves activity but also enhances stability. We have already demonstrated the superior antimycobacterial and antileishmanial activity of a range of alkyl C-galactofuranosides.5 Nevertheless, accessing such molecules requires toxic catalysts, multi-step syntheses or protecting group manipulations. Alternatively, eco-friendly routes have been reported but are limited to pyranosides. Thus, no selective synthesis of bioactive C-hexofuranoconjugates exists using eco-friendly procedures.
In this context, the thesis project will focus on developing environmentally friendly alternatives based on enzyme-catalyzed reactions under mild conditions in aqueous media. Already, glycoenzyme engineering has enabled tailoring glycoside hydrolases activity toward O- or S- glycosylation but not C-glycosylation.6 The PhD project aims to overcome these limitations by creating a novel enzymatic reactivity: C-glycoligation. Specifically, we will engineer the catalytic pocket of an arabinofuranosidase by incorporating specific amino acids known to selectively activate the phenol ring, enabling C-glycosylation. This innovative approach will generate a diverse library of aryl C-furanosides for further biological evaluation against targeted microorganisms.
Methodology: During the thesis, the PhD student will produce and purify mutated enzymes using well-established molecular biology techniques within the host research team. The student will screen for the best mutants and reaction conditions to perform C-glycoligation on a model substrate before extending the strategy to other polyphenols.

Your Work Environment

The recruited PhD student will join the Organic Chemistry & Interfaces (COrInt) team at Rennes Institute of Chemical Sciences. The team focuses on designing and synthesizing molecules with High Potential for Innovation with applications in health and well-being, prioritizing sustainable chemistry. This thesis aligns with the team's Glycochemistry and Biocatalysis research axis, which combines organic chemistry and biochemical approaches to develop glycoconjugates of interest through biocatalytic synthesis strategies. The PhD student will work under the supervision of Dr Laurent Legentil (full-time CNRS researcher) and the co-supervision of Dr Sylvain Tranchimand (associate professor at the Rennes School of Chemistry). The project is funded by the French National Research Agency (ANR PRC 2025 ProSacc) and involves collaboration with a research group in Nantes (Unit in Biological Sciences and Biotechnology). The successful candidate will benefit from a dynamic and well-equipped research environment, including state-of-the-art analytical and synthesis tools (LC-MS, 600 MHz NMR, parallel synthesis platform). The enzymes will be produced in-house in our dedicated molecular biology laboratory, a unique facility within the Chemistry Institute.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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