Email : joelle [dot] vidal [at] univ-rennes1 [dot] fr
Phone : +33 (0) 2 23 23 57 33
Office number : Beaulieu 10A, Office 160
- Design, synthesis and enzymatic evaluation of proteasome inhibitors
- Stereoselective synthesis of amino-acids
- Organic synthesis
- Electrophilic amination
- Chemistry of heterocycles
Key words / Scientific skills
- Peptide synthesis
- Protease inhibition
- Organic chemistry
- Medicinal chemistry
Education and professional experience
- Professor (2000- ), Université de Rennes 1
- Assistant professor, (1989-2000), Ecole normale supérieure de Lyon
- PhD, Université de Paris Sud
- Organic chemistry (3rd and 4th year students in chemistry)
- General chemistry (2nd year students in biology)
- Chemistry of amino-acids and peptides for chemistry students (master degree)
- General and organic chemistry for students in teacher education (master degree)
- Head of the first year and co-director of the master in chemistry since 2017.
Membership in professional organizations
- Société chimique de France (since 1992)
- American chemical society (since 1997)
- Union des professeurs de physique et chimie (since 1984)
Our group is involved in the design and the synthesis of original proteasome inhibitors to be used as drugs. The ubiquitin-proteasome pathway is the major proteolytic system responsible for intracellular proteolysis (Nobel Prize 2004). It is implicated in numerous pathological processes such as cancer, muscular dystrophies, inflammatory and immune diseases. Hence the proteasome inhibition is an efficient therapeutic approach. Three potent proteasome inhibitors are already approved for treating cancer. All these molecules are covalent inhibitors. Our goal is to develop less extensively studied non-covalent proteasome inhibitors that should have fewer side effects in therapeutics.
We have discovered and developed mainly two families of inhibitors. The first non-electrophilic organic small molecules that reversibly and non-covalently inhibit the proteasome have been discovered (collaboration with M. Reboud-Ravaux and B. O. Villoutreix, Paris). The development of linear tripeptide analogs of the natural TMC-95 led to the first X-ray structure of a non-covalent peptide inhibitor in complex with yeast protesaome (collaboration with M. Groll, Munich) and to fluorescent probes targeting the proteasome in cellulo. Bivalent inhibitors interacting simultaneously with two active sites of the proteasome were also synthesized and were very potent inhibitors of the chymotrypsin like and the trypsin like activities of the proteasome. Several noncovalent inhibitors are active against cancer cells.
Chemistry of 2-oxindole derivatives
In the course of the synthesis of oxotryptophane inhibitors of the proteasome, we have developed the chemistry of 3-hydroxy-2-oxindole derivatives.
Selected scientific production
Guy, L.; Vidal, J.; Collet, A.; Amour, A.; Reboud-Ravaux, M., Design and synthesis of hydrazinopeptides and their evaluation as human leukocyte elastase inhibitors. J. Med. Chem. 1998, 41 (24), 4833-4843. doi: 10.1021/jm980419o
Hannachi, J. C.; Vidal, J.; Mulatier, J. C.; Collet, A., Electrophilic amination of amino acids with N-Boc-oxaziridines: Efficient preparation of N-orthogonally diprotected hydrazino acids and piperazic acid derivatives. J. Org. Chem. 2004, 69 (7), 2367-2373. doi: 10.1021/jo035700b
Genin, E.; Reboud-Ravaux, M.; Vidal, J., Proteasome inhibitors: recent advances and new perspectives in medicinal chemistry. Curr. Top. Med. Chem. 2010, 10 (3), 232-256. doi: 10.2174/156802610790725515
Desvergne, A.; Genin, E.; Maréchal, X.; Gallastegui, N.; Dufau, L.; Richy, N.; Groll, M.; Vidal, J.; Reboud-Ravaux, M., Dimerized linear mimics of a natural cyclopeptide (TMC-95A) are potent noncovalent inhibitors of the eukaryotic 20S proteasome. J. Med. Chem. 2013, 56 (8), 3367-3378. doi: 10.1021/jm4002007
Richy, N.; Sarraf, D.; Maréchal, X.; Janmamode, N.; Le Guével, R.; Genin, E.; Reboud-Ravaux, M.; Vidal J., Structure-based design of human immuno- and constitutive proteasomes inhibitors Eur. J. Med. Chem. 2018, 145, 570-587. doi: 10.1016/j.ejmech.2018.01.013
BINOL derivatives-catalysed enantioselective allylboration of isatins: application to the synthesis of (R)-chimonamidine, J. Braire, V. Dorcet, J. Vidal, C. Lalli, F. Carreaux Org. & Biomol. Chem. 2020, 18 (31), 6042-6046, doi.org/10.1039/D0OB01386B
Book Chapter: Vidal, J., Synthesis and chemistry of α-hydrazino acids. In Amino Acids, Peptides and Proteins in Organic Chemistry, Hughes, A., Ed. Wiley-VCH: 2009; Vol. 2, pp 35-92.
Publications referenced in HAL :