7 research outputs found
DĂ©veloppement de la radiosynthĂšse de la [ÂčÂčC] sulfasalazine et du radiomarquage au fluor-18 d'aminoesters via un aziridinium pour l'imagerie TEP
Aminoacid transporters are often overexpressed in tumour cells and they represent molecular targets of choice for cancer imaging by Positron Emission Tomography (PET). In order to access to specific radiotracers of these transporters, the thesis project aimed at developing â in a first part, a new 18F-radiolabeling method of fluoroaminoacids based on deoxyradiofluorination of hydroxyaminoester precursors via an aziridinium intermediate â and in a second part, the radiolabelling with carbon-11 of sulfasalazine, an selective inhibiter of Xc- transporters. Deoxyradiofluorination reaction of stable and easily accessible hydroxyaminoesters possessing a serine, methylserine or hydroxyphenylalanine moiety, led to [18F]fluoroaminoesters at room temperature in high and reproducible radiochemical yields. Regioselectivity was function of the substituents on aziridinium ring and amine function. The radiosynthesis of [11C]sulfasalazine has been successfully achieved by coupling reaction of an appropriate diazonium salt with [11C]salicylic acid, obtained by [11C]carboxylation of a bismagnesium precursor from iodophenol. The automation of the radiosynthesis is in progress to produce [11C]sulfasalazine for in vivo studies.Les transporteurs dâacides aminĂ©s sont trĂšs souvent surexprimĂ©s au niveau des cellules tumorales et reprĂ©sentent une cible molĂ©culaire privilĂ©giĂ©e pour lâimagerie TEP (Tomographie par Emission de Positons) des cancers. Dans le but dâaccĂ©der Ă des radiotraceurs spĂ©cifiques de ces transporteurs, les travaux de thĂšse ont consistĂ© Ă mettre au point - dans une premiĂšre partie, une nouvelle mĂ©thode de marquage au fluor-18 dâacides aminĂ©s fluorĂ©s basĂ©e sur la dĂ©oxyradiofluoration de prĂ©curseurs hydroxyaminoesters, via un intermĂ©diaire aziridinium, - et dans une seconde partie, le marquage au carbone-11 de la sulfasalazine, un inhibiteur sĂ©lectif des transporteurs Xc-. La rĂ©action de dĂ©oxyradiofluoration des hydroxyaminoesters de structure sĂ©rine, mĂ©thylsĂ©rine ou hydroxyphĂ©nylalanine, facilement accessibles et stables, a permis dâobtenir Ă tempĂ©rature ambiante les [18F]fluoroaminoesters correspondants avec efficacitĂ© et reproductibilitĂ©. La rĂ©giosĂ©lectivitĂ© de la rĂ©action a Ă©tĂ© trouvĂ©e dĂ©pendante des substituants du cycle aziridinium et de la fonction amine. La radiosynthĂšse de la [11C]-sulfasalazine a Ă©tĂ© rĂ©alisĂ©e avec succĂšs par couplage dâun sel de diazonium appropriĂ© avec lâacide [11C]salicylique obtenu par rĂ©action de [11C]carboxylation dâun prĂ©curseur bismagnĂ©sien issu du iodophĂ©nol. Lâautomatisation de cette radiosynthĂšse est en cours dâoptimisation afin de produire la [11C]sulfasalazine en quantitĂ© suffisante pour rĂ©aliser les Ă©tudes in vivo
DĂ©veloppement de la radiosynthĂšse de la [ÂčÂčC] sulfasalazine et du radiomarquage au fluor-18 d'aminoesters via un aziridinium pour l'imagerie TEP
Aminoacid transporters are often overexpressed in tumour cells and they represent molecular targets of choice for cancer imaging by Positron Emission Tomography (PET). In order to access to specific radiotracers of these transporters, the thesis project aimed at developing â in a first part, a new 18F-radiolabeling method of fluoroaminoacids based on deoxyradiofluorination of hydroxyaminoester precursors via an aziridinium intermediate â and in a second part, the radiolabelling with carbon-11 of sulfasalazine, an selective inhibiter of Xc- transporters. Deoxyradiofluorination reaction of stable and easily accessible hydroxyaminoesters possessing a serine, methylserine or hydroxyphenylalanine moiety, led to [18F]fluoroaminoesters at room temperature in high and reproducible radiochemical yields. Regioselectivity was function of the substituents on aziridinium ring and amine function. The radiosynthesis of [11C]sulfasalazine has been successfully achieved by coupling reaction of an appropriate diazonium salt with [11C]salicylic acid, obtained by [11C]carboxylation of a bismagnesium precursor from iodophenol. The automation of the radiosynthesis is in progress to produce [11C]sulfasalazine for in vivo studies.Les transporteurs dâacides aminĂ©s sont trĂšs souvent surexprimĂ©s au niveau des cellules tumorales et reprĂ©sentent une cible molĂ©culaire privilĂ©giĂ©e pour lâimagerie TEP (Tomographie par Emission de Positons) des cancers. Dans le but dâaccĂ©der Ă des radiotraceurs spĂ©cifiques de ces transporteurs, les travaux de thĂšse ont consistĂ© Ă mettre au point - dans une premiĂšre partie, une nouvelle mĂ©thode de marquage au fluor-18 dâacides aminĂ©s fluorĂ©s basĂ©e sur la dĂ©oxyradiofluoration de prĂ©curseurs hydroxyaminoesters, via un intermĂ©diaire aziridinium, - et dans une seconde partie, le marquage au carbone-11 de la sulfasalazine, un inhibiteur sĂ©lectif des transporteurs Xc-. La rĂ©action de dĂ©oxyradiofluoration des hydroxyaminoesters de structure sĂ©rine, mĂ©thylsĂ©rine ou hydroxyphĂ©nylalanine, facilement accessibles et stables, a permis dâobtenir Ă tempĂ©rature ambiante les [18F]fluoroaminoesters correspondants avec efficacitĂ© et reproductibilitĂ©. La rĂ©giosĂ©lectivitĂ© de la rĂ©action a Ă©tĂ© trouvĂ©e dĂ©pendante des substituants du cycle aziridinium et de la fonction amine. La radiosynthĂšse de la [11C]-sulfasalazine a Ă©tĂ© rĂ©alisĂ©e avec succĂšs par couplage dâun sel de diazonium appropriĂ© avec lâacide [11C]salicylique obtenu par rĂ©action de [11C]carboxylation dâun prĂ©curseur bismagnĂ©sien issu du iodophĂ©nol. Lâautomatisation de cette radiosynthĂšse est en cours dâoptimisation afin de produire la [11C]sulfasalazine en quantitĂ© suffisante pour rĂ©aliser les Ă©tudes in vivo
Development of radiolabelling method with fluoride-18 of fluoroaminoesters via aziridinium intermediate and radiosynthesis of [11C]sulfasalazine for PET imaging
Les transporteurs dâacides aminĂ©s sont trĂšs souvent surexprimĂ©s au niveau des cellules tumorales et reprĂ©sentent une cible molĂ©culaire privilĂ©giĂ©e pour lâimagerie TEP (Tomographie par Emission de Positons) des cancers. Dans le but dâaccĂ©der Ă des radiotraceurs spĂ©cifiques de ces transporteurs, les travaux de thĂšse ont consistĂ© Ă mettre au point - dans une premiĂšre partie, une nouvelle mĂ©thode de marquage au fluor-18 dâacides aminĂ©s fluorĂ©s basĂ©e sur la dĂ©oxyradiofluoration de prĂ©curseurs hydroxyaminoesters, via un intermĂ©diaire aziridinium, - et dans une seconde partie, le marquage au carbone-11 de la sulfasalazine, un inhibiteur sĂ©lectif des transporteurs Xc-. La rĂ©action de dĂ©oxyradiofluoration des hydroxyaminoesters de structure sĂ©rine, mĂ©thylsĂ©rine ou hydroxyphĂ©nylalanine, facilement accessibles et stables, a permis dâobtenir Ă tempĂ©rature ambiante les [18F]fluoroaminoesters correspondants avec efficacitĂ© et reproductibilitĂ©. La rĂ©giosĂ©lectivitĂ© de la rĂ©action a Ă©tĂ© trouvĂ©e dĂ©pendante des substituants du cycle aziridinium et de la fonction amine. La radiosynthĂšse de la [11C]-sulfasalazine a Ă©tĂ© rĂ©alisĂ©e avec succĂšs par couplage dâun sel de diazonium appropriĂ© avec lâacide [11C]salicylique obtenu par rĂ©action de [11C]carboxylation dâun prĂ©curseur bismagnĂ©sien issu du iodophĂ©nol. Lâautomatisation de cette radiosynthĂšse est en cours dâoptimisation afin de produire la [11C]sulfasalazine en quantitĂ© suffisante pour rĂ©aliser les Ă©tudes in vivo.Aminoacid transporters are often overexpressed in tumour cells and they represent molecular targets of choice for cancer imaging by Positron Emission Tomography (PET). In order to access to specific radiotracers of these transporters, the thesis project aimed at developing â in a first part, a new 18F-radiolabeling method of fluoroaminoacids based on deoxyradiofluorination of hydroxyaminoester precursors via an aziridinium intermediate â and in a second part, the radiolabelling with carbon-11 of sulfasalazine, an selective inhibiter of Xc- transporters. Deoxyradiofluorination reaction of stable and easily accessible hydroxyaminoesters possessing a serine, methylserine or hydroxyphenylalanine moiety, led to [18F]fluoroaminoesters at room temperature in high and reproducible radiochemical yields. Regioselectivity was function of the substituents on aziridinium ring and amine function. The radiosynthesis of [11C]sulfasalazine has been successfully achieved by coupling reaction of an appropriate diazonium salt with [11C]salicylic acid, obtained by [11C]carboxylation of a bismagnesium precursor from iodophenol. The automation of the radiosynthesis is in progress to produce [11C]sulfasalazine for in vivo studies
DĂ©veloppement de la radiosynthĂšse de la [ÂčÂčC] sulfasalazine et du radiomarquage au fluor-18 d'aminoesters via un aziridinium pour l'imagerie TEP
Aminoacid transporters are often overexpressed in tumour cells and they represent molecular targets of choice for cancer imaging by Positron Emission Tomography (PET). In order to access to specific radiotracers of these transporters, the thesis project aimed at developing â in a first part, a new 18F-radiolabeling method of fluoroaminoacids based on deoxyradiofluorination of hydroxyaminoester precursors via an aziridinium intermediate â and in a second part, the radiolabelling with carbon-11 of sulfasalazine, an selective inhibiter of Xc- transporters. Deoxyradiofluorination reaction of stable and easily accessible hydroxyaminoesters possessing a serine, methylserine or hydroxyphenylalanine moiety, led to [18F]fluoroaminoesters at room temperature in high and reproducible radiochemical yields. Regioselectivity was function of the substituents on aziridinium ring and amine function. The radiosynthesis of [11C]sulfasalazine has been successfully achieved by coupling reaction of an appropriate diazonium salt with [11C]salicylic acid, obtained by [11C]carboxylation of a bismagnesium precursor from iodophenol. The automation of the radiosynthesis is in progress to produce [11C]sulfasalazine for in vivo studies.Les transporteurs dâacides aminĂ©s sont trĂšs souvent surexprimĂ©s au niveau des cellules tumorales et reprĂ©sentent une cible molĂ©culaire privilĂ©giĂ©e pour lâimagerie TEP (Tomographie par Emission de Positons) des cancers. Dans le but dâaccĂ©der Ă des radiotraceurs spĂ©cifiques de ces transporteurs, les travaux de thĂšse ont consistĂ© Ă mettre au point - dans une premiĂšre partie, une nouvelle mĂ©thode de marquage au fluor-18 dâacides aminĂ©s fluorĂ©s basĂ©e sur la dĂ©oxyradiofluoration de prĂ©curseurs hydroxyaminoesters, via un intermĂ©diaire aziridinium, - et dans une seconde partie, le marquage au carbone-11 de la sulfasalazine, un inhibiteur sĂ©lectif des transporteurs Xc-. La rĂ©action de dĂ©oxyradiofluoration des hydroxyaminoesters de structure sĂ©rine, mĂ©thylsĂ©rine ou hydroxyphĂ©nylalanine, facilement accessibles et stables, a permis dâobtenir Ă tempĂ©rature ambiante les [18F]fluoroaminoesters correspondants avec efficacitĂ© et reproductibilitĂ©. La rĂ©giosĂ©lectivitĂ© de la rĂ©action a Ă©tĂ© trouvĂ©e dĂ©pendante des substituants du cycle aziridinium et de la fonction amine. La radiosynthĂšse de la [11C]-sulfasalazine a Ă©tĂ© rĂ©alisĂ©e avec succĂšs par couplage dâun sel de diazonium appropriĂ© avec lâacide [11C]salicylique obtenu par rĂ©action de [11C]carboxylation dâun prĂ©curseur bismagnĂ©sien issu du iodophĂ©nol. Lâautomatisation de cette radiosynthĂšse est en cours dâoptimisation afin de produire la [11C]sulfasalazine en quantitĂ© suffisante pour rĂ©aliser les Ă©tudes in vivo
Deoxyradiofluorination Reaction from ÎČâHydroxyâαâaminoesters: an Entry to [18F]Fluoroaminoesters under mild conditions
LDM TEPInternational audienc
Radiosynthesis of [18F]Fluoroaminoesters by Deoxyradiofluorination of -Hydroxy--aminoesters under mild conditions
LDM-TEPInternational audienc
Structural features of the interaction of MapZ with FtsZ and membranes in Streptococcus pneumoniae
International audienceMapZ localizes at midcell and acts as a molecular beacon for the positioning of the cell division machinery in the bacterium Streptococcus pneumoniae. MapZ contains a single transmembrane helix that separates the C-terminal extracellular domain from the N-terminal cytoplasmic domain. Only the structure and function of the extracellular domain is known. Here, we demonstrate that large parts of the cytoplasmic domain is intrinsically disordered and that there are two regions (from residues 45 to 68 and 79 to 95) with a tendency to fold into amphipathic helices. We further reveal that these regions interact with the surface of liposomes that mimic the Streptococcus pneumoniae cell membrane. The highly conserved and unfolded N-terminal region (from residues 17 to 43) specifically interacts with FtsZ independently of FtsZ polymerization state. Moreover, we show that MapZ phosphorylation at positions Thr67 and Thr68 does not impact the interaction with FtsZ or liposomes. Altogether, we propose a model in which the MapZ-mediated recruitment of FtsZ to mid-cell is modulated through competition of MapZ binding to the cell membrane. The molecular interplay between the components of this tripartite complex could represent a key step toward the complete assembly of the divisome