Team description

The Symbiose group iscomposed of organicchemists (9 permanent members) fromCEISAMlaboratory (LabChimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation) in Nantes. It is involved in a number of academic and industrial research programs on multistep synthesis of natural compounds and analogues with potential biological or therapeutic applications. In this context, novel reactions or mechanisms of reaction in heterochemistry or radical chemistry are also studied. These last years, the activity of the group has been directed towards the synthesis of new alkaloids (nicotinic analogues), of complexe polycyclic molecules (angucycline or Peloruside A analogues), of supramolecular buildings (oligoheterocycles as foldamers), of novel nucleosides (siRNAs, INTIs..), and in a large part in the synthesis of glycoside derivatives. In this last area, the synthesis of analogues of a-GalCer, a glycosylceramide known as a potent immunostimulator and anticancer agent, has been developed. This work funded by the Cancéropôle Grand Ouest network, the ARC and an ANR program (collaboration with Dr J. Le Pendu (INSERM U862) and J.Y. Douillard (PHU)) has given promising results in term of activity and specificity, and some preliminary results have been patented. The efficient and modulable synthetic strategy to access to those glycosylceramides has been extended to the elaboration of another family of glycolipids designed as potential ion channels modulators. A partnership program has been established with a major pharmaceutical company for two years (2015).

Role in the network

A new class of efficient SK3 channel inhibitors has been synthesized by the team 6 (Pr P. A. Jaffres, Brest). The chemical structure of these molecules is characterized by the presence of a lipophylic chain fixed on a glycerol moiety, which one is bounded to a hydrophylic sugar head. One compound named Ohmline has been identified as a potent SK3 channel modulator. Based on its experience in glycochemistry (sugar and iminosugar) the Symbiose group has proposed to develop two families of amphiphilic molecules such as galactosylsphingosine and azasugar compounds, with similar chemical characteristics compared to Edelfosine or Ohmline, that means a polar head and hydrophobic tail. These compounds will be tested on a panel of ion channels including calcium-activated K+ channel SK3. The pharmacomodulations will be first done on the lipophilic chain to quickly furnish a series of compounds and in a second time on the sugar or aza cycles.

Involvement in tasks 6

 Discovery of SK3 channel and SOC modulators : Glycolipid analogs.

Valorizations/Collaborations

Publications / Patents

Linked to network

Synthesis of 3,4-dideoxy-3-fluoro- and 3,4-dideoxy-3,3-difluoro-KRN7000 Analogues: Comparison in Inducing CD1d-mediated Responses in Mice and Human iNKT Cells. Hunault, J. Diswall, M. Blot, B. Rocher, J. Marionneau, S. Oullier, T. Douillard, J.-Y.;Guillarme, S.; Saluzzo, C. Dujardin G. Jacquemin, D. Graton, J. Lequestel J-Y.Evain M. Lebreton J. Le Pendu J. Dubreuil, D. and Pipelier,M. J. Med. Chem. 2012, 55, 1227-1241.

New synthesis and characterisation of alternated ter-pyridine-bis-pyrrole strands as potent nitrogen-based donor/acceptor ligands. Tabatchnik-Rebillon A. Aubé C. Bakkali H. Delaunay T. ThiaManh G. Blot V. Thobie-Gautier C. Renault E. Planchat A. Le Questel J.-Y. Kauffmann B. Ferrand Y. Huc I. Urgin K. Condon S. Léonel E. Evain M.Lebreton J. Jacquemin D. Pipelier M. and Dubreuil, D. Chem. Eur. J.2010, 16, 11876-11889.

Rapid Access to (±)-Sedamine and some Original N-benzylated Unsaturated Analogues. A. Boussonnière, T. Ranaivondrambola, , J. Lebreton, M. Mathé-Allainmat. Synthesis, 2010, 14, 2456-2462.

Team publication