Equipe Transport et métabolisme de l'iode
Yves AMBROISE
CEA Saclay/Bât. 547
Tél: (33) 01 69 08 24 70
yves.ambroise@cea.fr
CEA Saclay/Bât. 547
Tél: (33) 01 69 08 24 70
yves.ambroise@cea.fr
Notre équipe s'intéresse à l'identification et l'utilisation des petites molécules pour élucider des mécanismes biologiques complexes.
Moyens humains
Yves AMBROISE, Chercheur
Fanny WALTZ, Doctorante
Pierre LACOTTE, Doctorant.
Thèmes de recherche
Un des projets concerne l'étude des mécanismes du transport de l'iode dans la thyroïde en utilisant les techniques de criblage à haut-débit, de flux isotopique et de "génétique chimique". Nous avons identifié les premiers modulateurs du transport de l'iode dans le thyrocyte. Ces molécules sont à l'heure actuelle utilisées comme outils pour l'identification de nouveaux effecteurs et/ou médiateurs du transport de l'iode (par photomarquage et chromatographie d'affinité). Par ailleurs, ces molécules sont aussi évaluées par imagerie in vivo comme outil de décorporation en cas de contamination à l'iode radioactif (accident nucléaire...).
Un deuxième projet concerne l'étude des mécanismes de séquestration de l'iode par l'algue brune Laminaria Digitata. Nous utilisons les techniques de "génétique chimie inverse" en étudiant l'inhibition des iodo- et bromo-peroxydases à vanadium par des petites molécules. En parallèle, nous utilisons des techniques d'imagerie sub-cellulaire (nano-SIMS et microscpectroscopie d'absorption de rayons-X) pour identifier et quantifier les formes d'iode dans l'algue brune.
©CEA/Y. Ambroise
Un deuxième projet concerne l'étude des mécanismes de séquestration de l'iode par l'algue brune Laminaria Digitata. Nous utilisons les techniques de "génétique chimie inverse" en étudiant l'inhibition des iodo- et bromo-peroxydases à vanadium par des petites molécules. En parallèle, nous utilisons des techniques d'imagerie sub-cellulaire (nano-SIMS et microscpectroscopie d'absorption de rayons-X) pour identifier et quantifier les formes d'iode dans l'algue brune.
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Mots-clés
Iode, NIS, haloperoxydase, Laminaria digitata, thyroïde, criblage à haut-débit, molécules bioactives, photomarquage d’affinité, génétique chimique.
Publications
Waltz F, Pillette L, Verhaeghe E, Ambroise Y. (2011). Synthesis and Structure-Activity Relationships of a Class of Sodium Iodide Symporter Function Inhibitors. ChemMedChem. 6, 1775-1777.
Waltz F, Pillette L, Ambroise Y. (2010) A non-radioactive iodide uptake assay for sodium iodide symporter function. Anal. Biochem. 396, 91-95.
Derbré S, Lecat-Guillet N., Pillon F, Ambroise Y. (2009). Synthesis and evaluation of photoreactive probes to elucidate iodide efflux in thyrocytes. Bioorg Med Chem Lett. 19, 825-7.
Lecat-Guillet N, Ambroise Y. (2009). Synthesis and evaluation of imidazo(2, 1-b)thiazole as iodide efflux inhibitors in thyrocytes. ChemMedchem. 4, 1819-1830.
Lindenthal S, Lecat-Guillet N, Ondo-Mendez A, Ambroise Y, Rousseau B, Pourcher T. (2009). Characterization of small-molecule inhibitors of the sodium iodide symporter. J Endocrinol. 200, 357-65..
Lecat-Guillet N, Ambroise Y. (2008). Discovery of Aryltrifluoroborates as Potent Sodium/Iodide Symporter (NIS) Inhibitors. ChemMedChem. 3, 1207-9.
Lecat-Guillet N, Ambroise Y. (2008). Enhanced iodide sequestration by 3-biphenyl-5,6-dihydroimidazo[2,1-b]thiazole in sodium/Iiodide symporter (NIS)-expressing cells. ChemMedChem. 3, 1211-6.
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.
Verhaeghe E, Buisson D, Zekri E, Leblanc C, Potin P, Ambroise Y. (2008). A colorimetric assay for steady-state analyses of iodo- and bromoperoxidase activities. Anal Biochem. 379, 60-5.
Lecat-Guillet N, Merer G, Lopez R, Pourcher T, Rousseau B, Ambroise Y. (2007). A 96-well automated radioiodide uptake assay for sodium/iodide symporter inhibitors. Assay Drug Dev Technol. 5, 535-40
Waltz F, Pillette L, Ambroise Y. (2010) A non-radioactive iodide uptake assay for sodium iodide symporter function. Anal. Biochem. 396, 91-95.
Derbré S, Lecat-Guillet N., Pillon F, Ambroise Y. (2009). Synthesis and evaluation of photoreactive probes to elucidate iodide efflux in thyrocytes. Bioorg Med Chem Lett. 19, 825-7.
Lecat-Guillet N, Ambroise Y. (2009). Synthesis and evaluation of imidazo(2, 1-b)thiazole as iodide efflux inhibitors in thyrocytes. ChemMedchem. 4, 1819-1830.
Lindenthal S, Lecat-Guillet N, Ondo-Mendez A, Ambroise Y, Rousseau B, Pourcher T. (2009). Characterization of small-molecule inhibitors of the sodium iodide symporter. J Endocrinol. 200, 357-65..
Lecat-Guillet N, Ambroise Y. (2008). Discovery of Aryltrifluoroborates as Potent Sodium/Iodide Symporter (NIS) Inhibitors. ChemMedChem. 3, 1207-9.
Lecat-Guillet N, Ambroise Y. (2008). Enhanced iodide sequestration by 3-biphenyl-5,6-dihydroimidazo[2,1-b]thiazole in sodium/Iiodide symporter (NIS)-expressing cells. ChemMedChem. 3, 1211-6.
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.
Verhaeghe E, Buisson D, Zekri E, Leblanc C, Potin P, Ambroise Y. (2008). A colorimetric assay for steady-state analyses of iodo- and bromoperoxidase activities. Anal Biochem. 379, 60-5.
Verhaeghe EF, Fraysse A, Guerquin-Kern JL, Wu TD, Devès G, Mioskowski C, Leblanc C, Ortega R, Ambroise Y, Potin P. (2008). Microchemical imaging of iodine distribution in the brown alga Laminaria digitata suggests a new mechanism for its accumulation. J Biol Inorg Chem. 13, 257-69.
Leblanc C, Colin C, Cosse A, Delage L, La Barre S, Morin P, Fievet B, Voiseux C, Ambroise Y, Verhaeghe E, Amouroux D, Donard O, Tessier E, Potin P. (2006). Iodine transfers in the coastal marine environment: the key role of brown algae and of their vanadium-dependent haloperoxidases. Biochimie. 88, 1773-1785.
Ambroise Y, and Boger DL. (2002). The DNA Phosphate Backbone Is Not Involved in Catalysis of the Duocarmycin and CC-1065 DNA Alkylation Reaction. Bioorg. Med. Chem. Lett., 12, 303–306.
Ambroise Y, Yaspan B, Ginsberg M, and Boger DL. (2002). Inhibitors of Cell Migration that Inhibit Intracellular Paxillin/α4 Binding: A Well Documented Use of Positional Scanning Libraries. Chemistry and Biology, 9, 1219–1226.
Faucher N, Ambroise Y, Cintrat JC, Doris E, Pillon F, Rousseau B. (2002). Highly chemoselective hydrogenolysis of iodoarenes. J Org Chem. 67, 932-934.
Goldberg J, Jin Q, Ambroise Y, Shigeki S, Desharnais J, Capps K, and Boger DL. (2002). Erythropoietin Mimetics Derived from Solution Combinatorial Library. J. Am. Chem. Soc., 124, 544–555.
Ambroise Y, Pillon F, Mioskowski C, Valleix A, Rousseau B. (2001). Synthesis and tritium labeling of new aromatic diazirine building blocks for photoaffinity labeling and cross-linking. Eur J Org Chem. 20, 3961-3964.
Boger DL, Goldberg J, Shigeki S, Ambroise Y, Cohen SB, and Vogt PK. (2000). Non Amide-Based Combinatorial Libraries Derived from N-Boc Iminodiacetic Acid : Solution Phase Synthesis of a 150-Member Piperazinone Library with Activity Against LEF-1/β-catenin Mediated Transcription. Helvet. Chim. Acta., 83, 1809–1845.
Ambroise Y, Mioskowski C, Djega-Mariadassou G, Rousseau B. (2000). Consequences of affinity in heterogeneous catalytic reactions: highly chemoselective hydrogenolysis of iodoarenes. J Org Chem. 65, 7183-7186.
Ambroise Y, Mioskowski C, Leblanc G, Rousseau B. (2000). Syntheses and properties of photoactivatable sugar derivatives designed to probe the sugar-binding site of melibiose permease. Bioorg Med Chem Lett. 10, 1125-1127.
Ambroise Y, Leblanc G, Rousseau B. (2000). Active-site-directed photolabeling of the melibiose permease of Escherichia coli. Biochemistry. 39, 1338-1345.
Ambroise Y, and Boger DL. (2002). The DNA Phosphate Backbone Is Not Involved in Catalysis of the Duocarmycin and CC-1065 DNA Alkylation Reaction. Bioorg. Med. Chem. Lett., 12, 303–306.
Ambroise Y, Yaspan B, Ginsberg M, and Boger DL. (2002). Inhibitors of Cell Migration that Inhibit Intracellular Paxillin/α4 Binding: A Well Documented Use of Positional Scanning Libraries. Chemistry and Biology, 9, 1219–1226.
Faucher N, Ambroise Y, Cintrat JC, Doris E, Pillon F, Rousseau B. (2002). Highly chemoselective hydrogenolysis of iodoarenes. J Org Chem. 67, 932-934.
Goldberg J, Jin Q, Ambroise Y, Shigeki S, Desharnais J, Capps K, and Boger DL. (2002). Erythropoietin Mimetics Derived from Solution Combinatorial Library. J. Am. Chem. Soc., 124, 544–555.
Ambroise Y, Pillon F, Mioskowski C, Valleix A, Rousseau B. (2001). Synthesis and tritium labeling of new aromatic diazirine building blocks for photoaffinity labeling and cross-linking. Eur J Org Chem. 20, 3961-3964.
Boger DL, Goldberg J, Shigeki S, Ambroise Y, Cohen SB, and Vogt PK. (2000). Non Amide-Based Combinatorial Libraries Derived from N-Boc Iminodiacetic Acid : Solution Phase Synthesis of a 150-Member Piperazinone Library with Activity Against LEF-1/β-catenin Mediated Transcription. Helvet. Chim. Acta., 83, 1809–1845.
Ambroise Y, Mioskowski C, Djega-Mariadassou G, Rousseau B. (2000). Consequences of affinity in heterogeneous catalytic reactions: highly chemoselective hydrogenolysis of iodoarenes. J Org Chem. 65, 7183-7186.
Ambroise Y, Mioskowski C, Leblanc G, Rousseau B. (2000). Syntheses and properties of photoactivatable sugar derivatives designed to probe the sugar-binding site of melibiose permease. Bioorg Med Chem Lett. 10, 1125-1127.
Ambroise Y, Leblanc G, Rousseau B. (2000). Active-site-directed photolabeling of the melibiose permease of Escherichia coli. Biochemistry. 39, 1338-1345.