PhD offer: Design and synthesis of multivalent epigenetic inhibitors

PhD offer in medicinal Chemistry and Chemical Biology

Glycochemistry and Molecular Recognition Team

Context and objective of the project – Epigenetic enzymes were identified as therapeutic targets in various diseases, including neurodegenerative diseases, schizophrenia, cancer and more recently in pulmonary and inflammation diseases. But selective targeting of epigenetic enzymes, e.g. HDACs, DNMT, and the understanding of the relative implication remain controversial and unaddressed.

In this context, the aim of this PhD project is to design and synthesis multivalent inhibitors to target specific epigenetic enzyme, based on crystal structure and known inhibitors, and decipher their roles in pathological contexts. First, single inhibitors will be functionalised to be grafted on various platform. Then, inhibition activity of the multivalent inhibitors will be measured and compare to single inhibitor. Finally, impact of the such inhibitors will be evaluated in cells.

Research team – This project will be carried out at the IBMM in the research group working in chemistry and chemical biology to decipher and target epigenetic mechanisms. This project is part of a collaborative project involving chemists, biochemists and biologists and the selected candidate will have the opportunity to take part of the biological evaluation of the compounds.

Funding – The candidate will have a CNRS contract funded through an ANR grant (MUSTARD project) for 36 months. This project is to start in October 2025.

Candidate – The candidate must have a training in organic chemistry and experience in synthesis of enzyme inhibitors and /or multivalent organic compounds. Experience in biological evaluation of active compounds would be appreciated but is not mandatory but the candidates must demonstrate interest for interdisciplinary project. Besides, candidates must be proactive for his/her project and be a team player with excellent communication skills.

To apply send a CV including 2 to 3 references (email and phone number) and a cover letter to Dr Marie Lopez ().