Missions

Synthesis of oligosaccharides of therapeutic interest

Shiga toxin-producing Escherichia coli (STEC) cause severe gastrointestinal infections ranging in severity from mild diarrhea to hemorrhagic colitis, which can progress to life-threatening hemolytic uremic syndrome (HUS). The E. coli O157:H7 serotype is the most frequently isolated in industrialized countries. One of the toxins appears to exhibit a preference for the P1 antigen (Galα1-4Galβ1-4GlcNAcβ1-3Galβ1-4Glc), and more specifically for the terminal trisaccharide Galα1-4Galβ1-4GlcNAc. This motif is therefore a key element for the design of compounds of therapeutic interest.

In this context, it is important to have access to these oligosaccharides of interest and possessing a reactive function in a non-reducing position of the allyl, 3-aminopropyl or propargyl type for subsequent conjugations on surfaces with a fluorophore or any other entity. The targeted oligosaccharides are therefore the terminal trisaccharide Galα1-4Galβ1-4GlcNAc and the complete pentasaccharide of the natural P1 antigen Galα1-4Galβ1-4GlcNAcβ1-3Galβ1-4Glc. The synthesis will be carried out through a synergy between organic (glyco)chemistry, developed at ICSN, and biotechnology, leveraging the expertise of the company Elicityl, to access the substructures of these oligosaccharides. A unified synthesis strategy will be based on access to large quantities (up to 1 kg) of N-acetyl-lactosamine and lactose by Elicityl, which represent the two starting materials necessary for these syntheses.

Activités

- Research, design, and develop chemical synthesis techniques adapted to the objectives of a scientific problem
- Participate in the development and conduct of research projects
- Select appropriate synthesis techniques; develop procedures and operating methods within the framework of a research project
- Coordinate or perform routine characterization of prepared products
- Validate data and interpret results
- Submit a quarterly written and oral report

Compétences

- Solid knowledge and experience in organic synthesis in inert media and at low temperatures
- Experience in multi-step synthesis
- Knowledge of spectrometry (UV)
- Good command of English (written)
- Writing and oral communication skills
- Team player

Contexte de travail

The Institute of Chemistry of Natural Substances is a CNRS Research Unit whose research focuses are chemistry and biology. It is part of the University of Paris-Saclay, which has brought together, since 2015, the research and teaching establishments of southern Paris. The ICSN is located on the Gif-sur-Yvette campus and has approximately 124 employees, including 71 permanent staff, spread over 3 buildings. Within the Chemobiology Department, the recruited employee will join the "Probes and Modulators for Biological Targets" team made up of approximately 15 people. He will be placed under the hierarchical authority of the team leader and the project will be carried out under the co-direction of Dr. Sébastien Vidal and Dr. Stéphanie Norsikian. The laboratory is equipped with all the necessary instruments for the project (HPLC, automatic flash chromatography, microwave synthesis reactor, freeze dryer, rotavap, etc.). Several analytical platforms are present in the institute and provide cutting-edge instruments: NMR (300, 500 MHz), mass spectrometry (LCMS, HRMS) and X-ray diffraction in particular.

Contraintes et risques

The project involves the Health and Safety constraints related to the handling of chemicals. The experiments will be carried out in a laboratory equipped with fume hoods.