Combinatorial chemistry and high throughput screening
Jean-Christophe CINTRAT
CEA Saclay/Bât 547
Tél: (+33) 1 69 08 25 70
Jean-Christophe.CINTRAT@cea.fr
CEA Saclay/Bât 547
Tél: (+33) 1 69 08 25 70
Jean-Christophe.CINTRAT@cea.fr
iBiTec-S / SCBM / LCB
Human resources
Jean-Christophe CINTRAT , Group Leader
Goulven MERER, Research Technician
Romain NOEL, Postdoctoral Fellow
Research Programs
Combining combinatorial chemistry and high-throughput screening (HTS) within our platform, we are interested in the discovery of new bio-active compounds. Those molecules discovered via HTS are then optimized using medicinal/combinatorial chemistry in order to produce new chemical tools for biological investigations, targets validation and/or new leads for future drugs developpement. New methodologies for access to targeted libraries are also developed.
We are involve in several collaborative projects with potential applications in drug discovery and biodefense.
Key words
High throughput screening, combinatorial chemistry, parallel synthesis, medical chemistry, application, anti-cancer and anti-malaria compounds
Publications
Botte C Y, Deligny M, Roccia A, Bonneau A L, Saidani N, Hardre H, Aci S, Yamaryo-Botte Y, Jouhet J, Dubots E, Loizeau K, Bastien O, Brehelin L, Joyard J, Cintrat J C, Falconet D, Block M A, Rousseau B, Lopez R, Marechal E. (2011). Chemical inhibitors of monogalactosyldiacylglycerol synthases in Arabidopsis thaliana. Nat Chem Biol. 7, 834-842.
Tarabout C, Roux S, Gobeaux F, Fay N, Pouget E, Meriadec C, Ligeti M, Thomas D, IJsselstijn M, Besselievre F, Buisson DA, Verbavatz JM, Petitjean M, Valery C, Perrin L, Rousseau B, Artzner F, Paternostre M, Cintrat JC. (2011). Control of peptide nanotube diameter by chemical modifications of an aromatic residue involved in a single close contact. Proc Natl Acad Sci U S A. 108, 7679-7684.
Mousseau G, Raffy Q, Thomas O P, Agez M, Thai R, Renault J P, Pin S, Ochsenbein F, Cintrat J C, Rousseau B. (2010). Footprinting of Protein Interactions by Tritium Labeling. Biochemistry. 49, 4297-4299.
Roux S, Ligeti M, Buisson DA, Rousseau B, Cintrat JC. (2010). Synthesis of orthogonally protected azahistidine: application to the synthesis of a GHK analogue. Amino Acids. 38, 279-286.
Traore T, Delacour L, Garcia-Argote S, Berthault P, Cintrat J C, Rousseau B. (2010). Scalable Synthesis of Cryptophane-1.1.1 and its Functionalization. Org Lett. 12, 960-962.
Yuen A K L, Lafon O, Charpentier T, Roy M, Brunet F, Berthault P, Sakellariou D, Robert B, Rimsky S, Pillon F, Cintrat J C, Rousseau B. (2010). Measurement of Long-Range Interatomic Distances by Solid-State Tritium-NMR Spectroscopy. J Am Chem Soc. 132, 1734-+.
Lecat-Guillet N, Merer G, Lopez R, Pourcher T, Rousseau B, Ambroise Y. (2008). Small-Molecule Inhibitors of Sodium Iodide Symporter Function. Chembiochem. 9, 889-95.
Lecat-Guillet N, Merer G, Lopez R, Pourcher T, Rousseau B, Ambroise Y. (2007). A 96-Well Automated Radio-Iodide Uptake Assay for Sodium/Iodide Symporter Inhibitors. Assay Drug Dev Technol. 5, 535-40.
Garcia-Saez I, DeBonis S, Lopez R, Trucco F, Rousseau B, Thuery P, Kozielski F. (2007). Structure of Eg5 in complex with a new monastrol-based inhibitor bound in the (R) configuration. J Biol Chem. 282, 9740-9747.
DeBonis S, Skoufias DA, Lebeau L, Lopez R, Robin G, Margolis RL, Wade RH, Kozielski F. (2004). In vitro screening for inhibitors of the human mitotic kinesin Eg5 with antimitotic and antitumor activities. Mol Cancer Ther. 3, 1079-1090.
brevets:
Lopez R, Rousseau B, Kozielski F, Skoufias DA, DeBonis S. (2005) Nouveaux derives dihydropyrimidines et leur utilisation comme agents anticancéreux. FR Patent 05-02518.
Lopez R, Rousseau B, Kozielski F, Skoufias DA, DeBonis S. (2006) Dihydropyrimidines and their use as anti-cancer agents. World Patent WO2006097617.
Deligny M, Saïdani N, Bonneau AL, Botté C, Hardre H, Rousseau B, Vial H, Mercier C, Lopez R, Maréchal E (2007).
Compounds with antiparasitic activity, applications thereof to the treatment of infectious diseases caused by apicomplexans. EP Patent, EP07290683.7
Bonneau AL, Botté C, Deligny M, Saïdani N, Hardre H, Rousseau B, Lopez R, Maréchal E (2007).
Use of compounds having a monogalactosyldiacylglycerol synthase inhibitory activity as herbicide or algaecide, herbicide and algaecide compositions. EP Patent, EP07290684.5
Tarabout C, Roux S, Gobeaux F, Fay N, Pouget E, Meriadec C, Ligeti M, Thomas D, IJsselstijn M, Besselievre F, Buisson DA, Verbavatz JM, Petitjean M, Valery C, Perrin L, Rousseau B, Artzner F, Paternostre M, Cintrat JC. (2011). Control of peptide nanotube diameter by chemical modifications of an aromatic residue involved in a single close contact. Proc Natl Acad Sci U S A. 108, 7679-7684.
Mousseau G, Raffy Q, Thomas O P, Agez M, Thai R, Renault J P, Pin S, Ochsenbein F, Cintrat J C, Rousseau B. (2010). Footprinting of Protein Interactions by Tritium Labeling. Biochemistry. 49, 4297-4299.
Roux S, Ligeti M, Buisson DA, Rousseau B, Cintrat JC. (2010). Synthesis of orthogonally protected azahistidine: application to the synthesis of a GHK analogue. Amino Acids. 38, 279-286.
Traore T, Delacour L, Garcia-Argote S, Berthault P, Cintrat J C, Rousseau B. (2010). Scalable Synthesis of Cryptophane-1.1.1 and its Functionalization. Org Lett. 12, 960-962.
Yuen A K L, Lafon O, Charpentier T, Roy M, Brunet F, Berthault P, Sakellariou D, Robert B, Rimsky S, Pillon F, Cintrat J C, Rousseau B. (2010). Measurement of Long-Range Interatomic Distances by Solid-State Tritium-NMR Spectroscopy. J Am Chem Soc. 132, 1734-+.
Lecat-Guillet N, Merer G, Lopez R, Pourcher T, Rousseau B, Ambroise Y. (2008). Small-Molecule Inhibitors of Sodium Iodide Symporter Function. Chembiochem. 9, 889-95.
Lecat-Guillet N, Merer G, Lopez R, Pourcher T, Rousseau B, Ambroise Y. (2007). A 96-Well Automated Radio-Iodide Uptake Assay for Sodium/Iodide Symporter Inhibitors. Assay Drug Dev Technol. 5, 535-40.
Garcia-Saez I, DeBonis S, Lopez R, Trucco F, Rousseau B, Thuery P, Kozielski F. (2007). Structure of Eg5 in complex with a new monastrol-based inhibitor bound in the (R) configuration. J Biol Chem. 282, 9740-9747.
DeBonis S, Skoufias DA, Lebeau L, Lopez R, Robin G, Margolis RL, Wade RH, Kozielski F. (2004). In vitro screening for inhibitors of the human mitotic kinesin Eg5 with antimitotic and antitumor activities. Mol Cancer Ther. 3, 1079-1090.
brevets:
Lopez R, Rousseau B, Kozielski F, Skoufias DA, DeBonis S. (2005) Nouveaux derives dihydropyrimidines et leur utilisation comme agents anticancéreux. FR Patent 05-02518.
Lopez R, Rousseau B, Kozielski F, Skoufias DA, DeBonis S. (2006) Dihydropyrimidines and their use as anti-cancer agents. World Patent WO2006097617.
Deligny M, Saïdani N, Bonneau AL, Botté C, Hardre H, Rousseau B, Vial H, Mercier C, Lopez R, Maréchal E (2007).
Compounds with antiparasitic activity, applications thereof to the treatment of infectious diseases caused by apicomplexans. EP Patent, EP07290683.7
Bonneau AL, Botté C, Deligny M, Saïdani N, Hardre H, Rousseau B, Lopez R, Maréchal E (2007).
Use of compounds having a monogalactosyldiacylglycerol synthase inhibitory activity as herbicide or algaecide, herbicide and algaecide compositions. EP Patent, EP07290684.5