327 research outputs found

    C-glycosyl compounds for bimodal PET/NIRF imaging. Application for RGD peptide labelling

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    Les travaux présentés dans cette thèse concernent des dérivés saccharidiques de type C-glycosidiques pour lesquels de nouvelles méthodologies synthétiques ainsi que des applications dans le domaine de l’imagerie TEP/FPIR ont été développées. Certains peptides possèdent un rôle majeur dans la thérapie et le diagnostic de diverses pathologies, le fait de les conjuguer à un fluorophore et un radioélément permet de réaliser des diagnostics précis et d’envisager des d’applications théranostiques par chirurgie. L’objectif a été de mettre au point la synthèse de sondes duales (radio)fluorées et fluorescentes pour l’imagerie bimodale TEP/FPIR. Ceci a nécessité une stratégie synthétique élaborée pour introduire un atome de fluor et un fluorophore de type cyanine, tous deux étant les sondes d’imagerie spécifiques TEP et FPIR. Deux stratégies principales ont été développées pour la synthèse de ces outils : la fonctionnalisation d’une plate-forme de type C-glycosidique comportant un motif [3.3.0]furofuranone et la fonctionnalisation d’une plate-forme de type C-glycosidique polyhydroxylée. Les stratégies de synthèse de type protection/déprotection ont permis la mise en place de ces divers éléments suivi de la conjugaison de deux peptides dérivés du RGD par réaction "Click" de type CuAAC. L’affinité de deux dérivés divalents fluorés et fluorescents vis à vis des intégrines est du même ordre de grandeur (40 nM) que celle du peptide seul, mettant en évidence le bénéfice de la divalence de l’agent. La radiofluoration d’une sonde duale a été réalisée avec succès permettant d’envisager des applications en imagerie in vivo par TEP et FPIR ainsi qu’en chirurgie guidée par fluorescence.The work developed in this thesis deals with C-glycosyl compounds for which new synthetic methodologies and applications in PET/NIRF imaging have been developed. Some peptides have a major role in the therapy and diagnostic of diverse pathologies and their conjugation with a fluorophore and a radioelement allow precise diagnostic and potential theranostic applications by surgery. The goal was to develop the synthesis of (radio)fluorinated and fluorescent dual probes for bimodal PET/NIRF imaging. An elaborated synthetic strategy was required to introduce a fluorine atom and a cyanine-type fluorophore, both being the specific probes of PET and NIRF imaging. Two main strategies were developed for the synthesis of these tools: the functionalization of C-glycosyl derivative including a [3.3.0]furofuranone scaffold and the functionalization of polyhydroxylated C-glycosyl compound. The protection/deprotection synthetic strategies have made possible the setting up of these various elements followed by the conjugation of two peptidic RGD derivatives by CuAAC “Click” reaction. The affinity of the two fluorinated and fluorescent derivatives for the integrins was in the same range (40 nM) than the RGD peptide alone, highlighting the benefit of the divalence of the agent. The radiofluorination of a dual PET/NIRF probe have been successfully achieved, allowing application for in vivo PET and NIRF imaging as well as NIRF-guided surgery

    Fluoro C-glycosides for peptides labeling : Applications in PET and dual PET/NIRF imaging

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    Les travaux développés dans cette thèse s’articulent autour de dérivés saccharidiques de type C-glycosides pour lesquels de nouvelles méthodologies synthétiques ainsi que des applications dans le domaine de l’imagerie TEP et TEP/FPIR ont été développées. Certains peptides possèdent un rôle majeur dans la thérapie et le diagnostic de diverses pathologies et le fait de les conjuguer à un dérivé saccharidique permet d’améliorer significativement leur biodistribution. La première partie de ce travail concerne la synthèse de C-glycosides fluorés (19F) et radiofluorés (18F) fonctionnalisés en position anomérique par un bras portant une fonction azide. Par réaction de cycloaddition 1,3-dipolaire, ces composés ont été couplés à des peptides dérivés de RGD, permettant ainsi le marquage de ces peptides par une méthode indirecte appelée stratégie prosthétique. La radiosynthèse d’un des radiotraceurs a été menée de manière complètement automatisée et l’évaluation biologique in vitro sur deux types d’intégrines et in vivo par imagerie TEP a pu mettre en évidence l’intérêt de ces radiotraceurs dans le domaine de l’oncologie. La seconde partie s’appuie sur ces premiers résultats concernant le développement de groupes prosthétiques saccharidiques pour aller plus loin en termes d’outils de diagnostic. L’objectif a été de mettre au point des sondes duales (radio)fluorées pour l’imagerie bimodale TEP/FPIR. Ceci a nécessité une stratégie synthétique élaborée pour introduire un atome de fluor et un fluorophore de type cyanine, tous deux étant les sondes d’imagerie spécifiques TEP et FPIR. L’accrochage d’une biomolécule (peptide RGD) a pu se faire là encore par réaction "Click". Des méthodes de fonctionnalisation régiosélectives ont permis la mise en place de ces divers éléments. Une perspective à ce travail sera d’évaluer les propriétés biologiques in vitro des outils synthétisés et de considérer cette sonde duale pour des applications diagnostique et théranostique en imagerie TEP/FPIR.The work developed in this thesis is based on saccharidic derivatives especially C-glycosides for which new synthetic methodologies and applications in the field of PET and PET/NIRF imaging have been developed. Some peptides play a major role in therapy and diagnosis of various pathologies and their conjugation with a saccharidic derivative significantly improves their biodistribution. The first part of this work concerns the synthesis of fluorinated (19F) and radiofluorinated (18F) C-glycosides fonctionalized in anomeric position by an arm bearing an azide function. These compounds were coupled by 1,3-dipolar cycloaddition to peptides derived from RGD, allowing the labeling of these peptides by an indirect method namely prosthetic strategy. The radiosynthesis of one radiotracer was fully automated. The in vitro biological evaluation on two types of integrins and in vivo by PET imaging showed the interest of these radiotracers in the field of oncology. The second part is closely linked to these first results. To go further in terms of diagnostic tools, dual (radio)fluorinated probes for bimodal PET/NIRF imaging were developed. This required an elaborated synthetic strategy to introduce a fluorine atom and a cyanine dye, both being PET and NIRF specific imaging probes. The coupling of a biomolecule (RGD peptide) was also performed by "Click" reaction. Regiocontrolled functionalization methods enabled the introduction of these various moieties. The perspective is to evaluate the in vitro biological properties of the synthetized tools and to consider this dual probe for diagnostic and theranostic applications in PET/NIRF imaging

    Dataset in support of the thesis 'The Effect of High-Fat Diet During Mouse Preimplantation and Pregnancy-Lactation on Uterine Fluid Protein Composition, Maternal Metabolism and Offspring Health''

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    Dataset and omic data from Thesis entitled: The Effect of High-Fat Diet During Mouse Preimplantation and Pregnancy-Lactation on Uterine Fluid Protein Composition, Maternal Metabolism and Offspring Health. Author: Irene Peral-Sanchez The added dataset included raw data generated from the period from Oct 2019 to December 2023. As explained in the thesis, the data were analyzed using SPSS syntax (hierarchical model) and Prism. The omics data (RNA seq and Proteomics) were additionally studied by String and Gene Ontology, apart from R (collaborators). If any other questions or clarification is needed, contact the author or main supervisor. </span

    Synthèse et réactivité de systèmes insaturés dihalogénés (applications en synthèse organique)

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    L'étude de la réactivité régio- et stéréosélective du bromure de bromobenzyle nous a permis de synthétiser des motifs styréniques métallés par un bras espaceur de 1 à 3 atomes de carbone ainsi que des motifs bis-aryles en présence de sels de palladuim (catalyse de type Stille ou Suzuki). La synthèse régio- et stéréosélective d'acides et dérivés insaturés b,g- ou a,b- dihalogénés équivalents à des systèmes tris-électrophiles nous a conduit à étudier la réactivité de ces synthons. L'étude de la réactivité par catalyse palladiées d'acides insaturés b,g-dihalogénés à conduit à la formation d'acide pyrrol-3-yl acétiques substitués, en une seule étape, selon une quadruple séquence. Ces acides ont permis de former des motifs 5H-furan-2-ones substitués en position 4, par cyclisation intramoléculaire puis couplages palladiés. Une série de différentes catalyses palladiées régio- et stéréosélective sur des acides insaturés a,b-dihalogénés, a permis d'obtenir des oléfines tri-substituées, notamment des précurseurs de dérivés du Naproxène ayant potentiellement des applications pharmaceutiques intéressantes et des motifs 3-alkylidène-4-halogéno-3H-furan-2-onesThe study of the regio- and stereo selective reactivity of the bromobenzyl bromide allowed us to synthesize styrenic compounds metaled with a space arm of 1 or 3 atoms of carbon and bi-arly compounds palladuim salts(Stille or Suzuki cross coupling). The selective synthesis of insaturated acids and esters b,g ou a,b-dihalogenated equivalents with tris-electrophils systems led us to study the reactivity of these compounds. The study of the reactivity of insaturated acids b,g-dihalogenated with palladuim cross coupling led to the formation of substituted pyrrol-3-yl acetics acids in one stage according to a triple sequence. these acids also made it possible to form 4-substituted pyrrol-3-yl acetics acids in one stage according to a triple sequence. These acids also made it possible to form 4-substituted-5H-furan-2-ones by intramolecular cyclisation and then cross coupling. A series of different selectivity palladuim cross coupling on insaturated acids a,b-dihalogenated allowed to obtain trisubstituted olefins, in particular precursors of derived from Naproxen having potentially interesting pharmaceuticals applications and 3-alkylidene-4-halogeno-3H-furan-2-onesTOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

    Retraction Note to: Omega-3 fatty acid levels in red blood cell membranes and physical decline over 3 years: longitudinal data from the MAPT study

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    International audienceThe Editors-in-Chief have retracted this articlebecause it contains text in the introduction and dis-cussion sections that overlaps with a previous pub-lished article by a different author group [1]. BertrandFougere, Christelle Cantet, Gaelle Soriano, SophieGuyonnet, Philipe De Souto Barreto, Matteo Cesari,Sandrine Andrieu and Bruno Vellas agree with thisretraction. Bertrand Fougere agrees with this retrac-tion on behalf of the MAPT Study Group. SabineGossier has not responded to correspondence fromthe publisher about this retraction

    ‘Sandrine Bonnaire regained’: space and mobility in Sans toit ni loi and Prendre le large.

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    This article considers the parallels that can be drawn between two characters portrayed by Sandrine Bonnaire at distinct junctures in her film career: Mona, a young homeless woman whose wanderings are recounted retrospectively after her frozen corpse is discovered at the start of Agnès Varda’s Sans toit ni loi/Vagabond (1985), and Édith, a middle-aged woman who relocates to Morocco to keep her job with an offshored French textile factory in Gaël Morel’s Prendre le large/Catch the Wind (2017). The author first considers Mona and Édith in the context of a stasis-mobility dynamic identified as central to both films, subsequently reflects on the political implications of their mobility and finally considers a more proximate notion of space, with reference to the theory of haptic visuality explored by Laura Marks (2000). Prendre le large illustrates the limits of the palimpsestic star image and, in counterpoint, the recuperative possibilities of a film depicting an immersive encounter with a foreign space. The article aims to demonstrate how the quite specific questions of labour and relocation broached in these films point to broader existential issues pertaining to identity and movement, as well as to consider what the two films, in dialogue with each other, might add to current debates around precarity in contemporary cinema

    How explosive are cryptocurrency prices?

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    The author gratefully acknowledges useful comments by Beat Hintermann, Xin Jin, as well as participants of the 18th Journees LAGV - International Conference in Public Economics. Furthermore, the author is indebted to Sandrine Ngo for motivating me to study the economics of Bitcoins

    Can Positional Concerns Enhance the Private provision of Public Goods?

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    The social welfare effect of positional concerns over public goods is composed of two parts, a positional outcome and an outcome in terms of public goods provision. When agents have homogenous positional preferences over the public good, they overinvest in the positional public good, resulting in a zero-sum positional race with a higher provision of the public good. When agents differ in their positional preferences, the overall impact on social welfare is positive when endowments are homogenous and uncertain when endowments are heterogeneous. Given that the social loss from position-seeking is lower than the social gain from rank seeking, there is an increase of social welfare. If agents have different initial endowments, positional preferences might still be welfare enhancing as long as the positional loss does not exceed the gain in terms of public good provision.

    Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

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    Efficient routes were developed for the diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues. The key steps of the synthesis were the easy accessibility of different types of arms in term of configuration (myo and scyllo), the linking method and length, which could modulate the biological properties. These inositol derivatives, bearing an arm terminated either with a hydroxy group or a fluorine atom, could be interesting candidates for diastereoisomeric intermediates and biological evaluations, especially for PET imaging experiments
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