Missions

In order to limit the side effects of treatments that are often burdensome for patients, the development of new targeted and effective therapeutic approaches remains a colossal challenge. In recent years, the discovery of bioorthogonal chemistry, which makes it possible to carry out specific and selective chemical reactions in vivo, has broadened the scope of these therapeutic approaches. These bioorthogonal reactions are compatible with the biological environment and take place selectively between two reaction partners that are inert to the numerous chemical functions potentially present in the biological environment. This research project will focus on the use of a new and original category of bioorthogonal reactions. These reactions, known as click and release, can be used to develop bifunctional systems for the controlled release of both an active principle (therapeutic) and a fluorescent molecule (diagnostic). This project will focus on the development of one of these reactions, involving a profluorescent tetrazine unit (diene) carried by a ligand of a receptor overexpressed in certain diseases, and a second partner (dienophile) containing a pro-fluorophore or pro-drug. The ligation and cleavage reaction will enable the fluorophore and drug to be released on demand. This new theranostic tool will be used both for imaging a patient's pathology and for the on-demand, controlled release of the active ingredient needed to treat the pathology, only at the site of interest, thereby minimising the treatment's side effects.

Activités

Main tasks:
- Synthesis and characterisation of reaction partners: pro-fluorescent tetrazine, dienophile
- Study of the bioorthogonal reaction: determination of kinetics and release efficiency - Analytical methods: HPLC; absorption (UV-VIS) and emission (fluorescence) spectroscopy.

Compétences

The candidate must hold a PhD in organic chemistry.
Required skills:
- ability to develop strategies for synthesising organic compounds
- mastery of organic molecule characterisation techniques and analysis methods
- good knowledge of the chemistry/biology interface

Desired skills:
- experience of fluorophore chemistry
- good writing skills, ability to publish and promote research work
- ability to work in a team

Contexte de travail

This research project will be carried out at the CARMeN Institute of the University of Rouen Normandy. The candidate will work in the Bioorganic Chemistry team under the supervision of the scientific leader(s) of the project.

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.

Contraintes et risques

Exposure to chemicals.