Transport and Metabolism of iodine
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
iBiTec-S / SCBM / LCB
Human resources
Yves AMBROISE, Group Leader
Fanny WALTZ, PhD student
Pierre LACOTTE, PhD Student
Research Programs
Our group focuses on the discovery and use of small organic molecules for the elucidation of complex biological mechanisms
We use high-throughput screening techniques, isotopic flux experiments, and “chemical genetics” methods to investigate iodine transport in the thyroid gland. We have discovered the firsts small molecules capable of modulating the iodide transport mediated by the Sodium/Iodide Symporter (NIS) in the thyrocyte. These molecules are currently used as chemical tools for the identification of iodide transport mediators (photo-labeling, affinity chromatography…). Besides, these molecules are evaluated in vivo for their potential applications in radio-iodide body decontamination (nuclear accident).
We also investigate the mechanisms by which the brown algae Laminaria Digitata accumulates and sequestrates huge amounts of iodide (30,000 fold). We use “reverse chemical genetics” methodologies and focuse more precisely on the iodo- and bromo-peroxidases inhibition by small molecules. In parallel, the ultra-structural iodine distribution in brown algae is investigated using ion beam micro-chemical imaging as well as nano-Secondary Ion Mass Spectrometry (nanoSIMS).
©CEA/Y. Ambroise
We use high-throughput screening techniques, isotopic flux experiments, and “chemical genetics” methods to investigate iodine transport in the thyroid gland. We have discovered the firsts small molecules capable of modulating the iodide transport mediated by the Sodium/Iodide Symporter (NIS) in the thyrocyte. These molecules are currently used as chemical tools for the identification of iodide transport mediators (photo-labeling, affinity chromatography…). Besides, these molecules are evaluated in vivo for their potential applications in radio-iodide body decontamination (nuclear accident).
We also investigate the mechanisms by which the brown algae Laminaria Digitata accumulates and sequestrates huge amounts of iodide (30,000 fold). We use “reverse chemical genetics” methodologies and focuse more precisely on the iodo- and bromo-peroxidases inhibition by small molecules. In parallel, the ultra-structural iodine distribution in brown algae is investigated using ion beam micro-chemical imaging as well as nano-Secondary Ion Mass Spectrometry (nanoSIMS).
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Key words
Iodine, NIS, haloperoxydase, Laminaria digitata, thyroid, high-throughput screening, bioactive molecules, photoaffinity labelling, chemical genetics.
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.