Дисертації з теми "Recherche de ligands"
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Dagher, Rania Haiech Jacques Pigault Claire. "Recherche de petites molécules bioactives sur la calmoduline outils de recherche pour analyser son rôle dans le signal calcique /." Strasbourg : Université de Strasbourg, 2009. http://eprints-scd-ulp.u-strasbg.fr:8080/1108/01/DAGHER_Rania_2008.pdf.
Le, Manach Claire. "Recherche de ligands du système tubuline/microtubules par chimie combinatoire dynamique." Paris 11, 2008. http://www.theses.fr/2008PA112340.
The system tubulin/microtubules plays a key-role during mitosis and disturbing its dynamic equilibrium can prevent cell division and induce apoptosis. Antitubulin agents are divided into two classes: those that bind to microtubules, stabilizing them and preventing their depolymerization, and those that bind to tubulin dimer, preventing the formation of microtubules. Most of the known antitubulin agents are characterized by a very complex structure, and therefore are relatively hard to synthesize. We planned to use dynamic combinatorial chemistry combined with the reversible formation of imines in water to identify new potential antitubulin agents. This approach is based on the reversible connection between different building blocks to form a chemical library under thermodynamic equilibrium. In the presence of a target, the distribution of the library may be altered, with an amplification for the best binders, which can be detected by an adequate analytical method after fixation of the library’s distribution. We have demonstrated that dynamic combinatorial chemistry is applicable to the dynamic macromolecular system tubulin/microtubules. Using adequate conditions, we have shown that it is possible to target either the tubulin dimer or microtubules. Then we have designed and synthesized two types of scaffolds in order to use them in dynamic libraries. Among the numerous dynamic libraries we prepared some amplifications were identified. Analogues of amplified imines were synthesized and tested on tubulin. Therefore we were able to identify a new class of microtubules ligands and to show that the orientation of two aromatic moieties plays a key role for the type of activity
Mossand, Guillaume. "Recherche de nouveaux ligands pour l'extraction sélective de l'uranium et des terres rares." Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAV053.
The supply of uranium-based nuclear fuel is a key issue of the electricity production strategy in France, especially as demand for natural uranium will continue to increase in the near future. Rare earths are also considered as strategic metals due to their remarkable properties which make them essential in many applications related to new technologies.There is therefore an interest in developing new, more efficient processes for the extraction of uranium and rare earths than those currently used. The aim is to respond to a permanent increase in demand for raw materials, against the backdrop of the development of new recycling processes, especially for rare earths.Through a multi-scale approach, this PhD thesis sets to develop novel organic ligands with a strong extractant ability for uranyl (UO22+) or for rare earths (TR3+), as well as a high selectivity with respect to various impurities, in particular iron (Fe3+). Thus, many ligands have been designed, synthesized and tested by liquid-liquid extraction in several acidic synthetic media. Bifunctional bi , tri- and pentadentate molecules have been developed and their complexing properties and their speciation in organic medium have been evaluated in the presence of UO22+ and Fe3+ by different approaches (DFT, UV-visible, IR, ESI-MS, EXAFS). Furthermore, several new ligands have been evaluated for the selective extraction of rare earths and the results obtained are remarkable. Overall, these studies have led in some cases to the development of novel molecular designs with excellent extractant properties. Their optimization, coupled with different analytical techniques, fulfilled the objectives of this thesis and will serve in the future to the development of new efficient and selective extractants
Dagher, Rania. "Recherche de petites molécules bioactives sur la calmoduline : Outils de recherche pour analyser son rôle dans le signal calcique." Université Louis Pasteur (Strasbourg) (1971-2008), 2008. https://publication-theses.unistra.fr/public/theses_doctorat/2008/DAGHER_Rania_2008.pdf.
Rogue, Alexandra. "Recherche de gènes cibles de ligands de PPARs et étude de leurs mécanismes d'action." Rennes 1, 2011. http://www.theses.fr/2011REN1B082.
DARDE-IMANI, VALERIE. "Recherche de nouveaux ligands selectifs serotoninergiques : synthese et activite d'analogues fluores de 2-amino-tetralines." Paris 6, 1995. http://www.theses.fr/1995PA066576.
Lawson, Marie. "Recherche de nouveaux ligands du site de la colchicine : Modélisation moléculaire, synthèse et évaluation biologique." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS069.
As part of this work we are interested in discovering new ligands original tubulin inhibitory activity having its polymerization. To do this, rational in silico study is performed to obtain the active molecules in vitro that protein. During this first year of thesis we have developed in collaboration with the modeling team BioCIS - CNRS (Dr. G. Bernadat and Prof. T. Duong Ha.) A virtual screening a chemical library of more than 3 million chemical structures in the ZINC database according to structural descriptors. This screening allowed us to bring out thirty of potentially active molecules. We have already synthesized a quarter of these molecules that are currently being biological evaluation in collaboration with the team of Biochemistry and Structural chemistry of natural substances (Dr. J. Bignon and Dr. J. Dubois) of The Institute Chemistry and Natural Products. For this year, we will continue the synthesis of molecules from this screening in order to assess their activities on tubulin. Depending on the laboratory results, we can also perform pharmacomodulations to improve any potential ligands
Marger, Fabrice. "Implication des canaux calciques de type T dans la douleur viscérale et recherche de ligands." Montpellier 1, 2009. http://www.theses.fr/2009MON1T006.
Poncet-Montange, Guillaume. "Études structurales et fonctionnelles de la NAD Kinase 1 de Listeria monocytogènes : vers une conception rationnelle de ligands utilisant une approche par fragment." Montpellier 1, 2007. http://www.theses.fr/2007MON13505.
The emergence of antibiotic resistance on the one hand, and the immense bulk of data produced by genome sequencing projects on the other, urge to rationalize and accelerate the search for new therapeutic targets. Thus, new methodologies need to be developed to speed up both the biochemical characterization and the determination of potential ligands. Here we used X-ray cristallography with focused combinatorial chemistry as an approach to efficiently determine inhibitors for the NAD kinases 1 from Listeria monocytogenes (NADK1Lm). We determined the high resolution crystallographic complex of NADK1Lm in its free state, and bound to several biological or artificial ligands. Our analysis allowed us 1) to characterize in detail the NAD binding site, 2) to improve the knowledge of the enzymatic mechanism 4) to discover a new nucleotide, the 2’phospho-ATP, with an unknow biological function and 4) to identify the first inhibitor for NADK1Lm, the di-(5’-thio-adenosine)
Podevin, Christelle. "Recherche de nouveaux ligands des récepteurs du système nerveux central : synthèse d'Aza B-norbenzomorphanes et dibenzodiacines à partir de quinoléines." Bordeaux 1, 1998. http://www.theses.fr/1998BOR10626.
Aza B-norbenzomorphans and dibenzodiazecines contain structural features for CNS receptor recognition. They are interesting targets, which could in the future lead to new ligands for opioid receptors imaging. A zinc-acetic acid promoted one pot reaction was proposed, and led to the pentacyclic diamines starting from substituted quinolines. This regio- and sometimes stereoselective reaction allowed us to access to 54 original compounds with good yields. In the same experimental conditions, the 4-picoline methiodide led to an original tetracyclic compound complexed with one molecule of ZnI₂. The whole series was submitted to a pharmacological screening. The results showed that N-acetyl aza B-norbenzomorphans produce a dose-dependent activity on opioid receptors while the N-allyl ones exhibit affinity for α-2 receptors
Savarin, Aline. "Ciblage de l'endothélium tumoral et inflammatoire : Recherche de ligands de la sélectine E et de l'endogline." Phd thesis, AgroParisTech, 2005. http://pastel.archives-ouvertes.fr/pastel-00005017.
Dodi, Alain. "Influence des complexants organiques sur le relâchement des métaux. Intérêt des techniques chromatographiques et électrophorétiques pour leur recherche." Aix-Marseille 3, 2008. http://www.theses.fr/2008AIX30075.
Organic complexants constitute a particular family of organic molecules, characterised by the property to form more or less stable complexes with metal cations. The first part of the thesis shows how these complexants support the mobilisation of the metal species, for example those which are present in a disposal of radioactive waste, or how they allow the remediation of polluted soils. In the second part of the document, we will show how certain complexants can be formed by radiolysis of organic materials present in nuclear waste packages. Thus, we show for example that 22 % in mass of cellulose constituting the cotton blouses is radiolysed in the form of leachable organic carbon, after an irradiation under 4,2 MGy. The third part describes the methodologies developed in order to allow the measurement of these organic complexants at low level. The implemented techniques are : - ionic chromatography which is applied to the measurement of mono and poly carboxylates and also to the breakdown products of tributylphosphate (TBP) : mono and dibutyl phosphate (MBP, DBP). Ion chromatography is also applied to the measurement of the amines resulting from the radiolytic degradation of ion exchange resins. - ion exclusion chromatography was primarily applied to carboxylate ions. - ion suppression chromatography and ion pairing chromatography were implemented in order to measure aminopolycarboxylic chelating molecules such as EDTA, NTA, DTPA and CDTA. - reverse phase liquid chromatography coupled with mass spectrometry through electrospray (ESI) and atmospheric pressure chemical ionisation (APCI) interfaces, was applied to the measurement of TBP, EDTA and to the degradation products of TBP (DBP and MBP). - capillary electrophoresis was applied to the measurement of carboxylic complexants and amines. The last part of the thesis relates to the development of a test which allows an assessment of the global complexing capacity of an aqueous solution. This test consists in the addition of a metallic cation weakly hydrolysable (Co2+) which will be complexed with the possible chelating molecules present in the solution. The metal complexes thus formed are anionic or neutral species in solution, and are thus retained over an anion exchanging resin, whereas uncomplexed Co (II) is eluated from the resin. The measurement of this eluated Co (II) then makes it possible to know the quantity of complexed Co (II) and consequently to determine the global complexing power (or capacity) of the solution. This complexing power being expressed for example in mmole (or mg) of Co complexed per litre of aqueous solution
Yous, Saïd. "Recherche de ligands des recepteurs de la melatonine : analogues naphtaleniques et produits de transformation des acyl-6 benzothiazolinones." Lille 2, 1991. http://www.theses.fr/1991LIL2T005.
Shen, Shuren. "La mélatonine : étude du récepteur et de l' enzyme de biosynthèse sérotonine-N-acétyltransférase por la recherche de nouvelles molécules à potentialité thérapeutique." Paris 5, 1995. http://www.theses.fr/1995PA05P631.
Olivieri, Lilian. "Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité." Thesis, La Réunion, 2012. http://www.theses.fr/2012LARE0011/document.
FKBP12 is an ubiquitous, mostly cytosolic, protein found at the crossroads of several signaling pathways. Its natural abundance in the nervous tissues can be related to its implication in neurodegenerative diseases like Alzheimer's and Parkinson's as well as in peripheral neuropathies and diabetes or in injuries of the spinal cords. Several studies have demonstrated that exogenous molecules (ligands) that can bind to FKBP12 allow the regeneration of many damaged neuron connections. However, there is no clear relationship between the structure of a ligand and its ability to bind to FKBP12. Our study aims at rationalizing the relationship between the structure of a ligand and its affinity to FKBP12. Two model complexes, formed between FKBP12 and each of the two high-affinity ligands 8 and 308, were studied. These two ligands are structurally different. We used molecular dynamics simulations to characterize the intermediate state that is transiently formed during the binding process between the protein and its ligand. In this state, the analysis of the nascent interactions allowed (i) to unravel the role played by the various ligand moieties in the recognition process with FKBP12 and (ii) to rationalize the affinities of related ligands
Fournier, Catherine. "Etude fonctionnelle du domaine sh3 des spectrines erythroides et non erythroides ; recherche de ligands par le systeme du double-hybride." Paris 7, 1998. http://www.theses.fr/1998PA077057.
Lesourd-Moulin, Valérie. "Les acides humiques et leurs interactions avec les éléments métalliques Cull, EuIII, ThIV, UVI : apport d'une méthode de chromatographie par exclusion sérique et recherche de modèles de complexation." Lyon 1, 1985. http://www.theses.fr/1985LYO10506.
Tafani, Jean André Mathieu. "Ligands radioiodés pour l'étude in vivo des récepteurs aux opioi͏̈des par tomographie d'émission monophotonique." Toulouse 3, 1993. http://www.theses.fr/1993TOU30233.
Daval, Sandrine. "Contribution à l'étude de la modulation allostérique du récepteur muscarinique M1 : recherche de modulateurs positifs originaux. Caractérisation de l'interaction de divers ligands fluorescents." Strasbourg, 2009. http://www.theses.fr/2009STRA6210.
Muscarinic receptors belong to the large GPCRs family. They are involved in a number of physio-pathological processes and are potential therapeutic targets. During my PhD thesis, I have much interest in the muscarinic M1 sub-type which is essentially expressed in the CNS and is of particular interest for the treatment of Alzheimer Disease or schizophrenia. First, the prestwick chemical library was screened in order to find novels positives allosteric modulators. Calcium mobilization was used as a functional read out, but only leads to identification of signaling pathway modulators. In a second time, the orthosteric/allosteric nature of Bodipy-pirenzepine derivatives/muscarinic M1 receptor interaction was studied. All bodipy-pirenzepine derivatives are bitopic ligands whatever the nature and the length of their linker. Finally, AC-42 fluorescent derivatives were developed and characterized as fluorescent allosteric tracer of the muscarinic M1 receptor
Perrot, Thomas. "Diversité fonctionnelle des systèmes de détoxication chez les champignons lignolytiques." Thesis, Université de Lorraine, 2018. http://www.theses.fr/2018LORR0140/document.
Wood decaying fungi play an important role in the carbon cycle by participating in the recycling of organic matter. In addition to their ability to mineralize lignocellulosic biomass, these organisms have the ability to degrade potentially toxic molecules released during this process. Their detoxification system involves several multigenic families including glutathione transferases. These ubiquitous enzymes are grouped into several classes in the fungal kingdom, some of them are widespread in these fungi. In this context, the main objective of this thesis was to understand the functions of glutathione transferases of the Omega class (GSTOs) extended in Trametes versicolor, a white rot fungus. A biochemical and structural approach was led using nine recombinant proteins. Firstly, enzymatic characterization of these isoforms was performed using synthetic substrates, the obtained results demonstrating a similarity of catalytic properties. Then, using a library of pure molecules and another one of complex mixtures from different forest species, a high throughput screening method was applied to identify potential ligands for these enzymes. The resolution of the three-dimensional structure of three isoforms demonstrated the homodimeric state of these proteins and the involvement of two binding sites in the recognition of these ligands: the H site (present in each monomer) and the L site (at the dimer interface). For example, the isoform TvGSTO3S is able to bind several hydroxybenzophenones in its H site, but also a flavonoid, dihydrowogonin. In this case, this interaction with a natural ligand derived from wild-cherry tree extract was demonstrated by an affinity crystallography approach. On the other hand, co-crystallization experiments detected two molecules of another flavonoid, naringenin, in the L site of the isoform TvGSTO6S. Finally, a specific interaction involving the H and L sites of the isoform TvGSTO2S was demonstrated with oxyresveratrol. Structural analysis revealed that the presence of both configurations of the stilbene in the protein: the trans configuration in the H site and the cis configuration in the L site. Thus, despite partial functional redundancy, this research demonstrated the existence of a specific pattern of interactions for each tested isoform. The expansion of the Omega class could indicate that these enzymes are involved in the adaptation of the fungus in its environment. Indeed, the ligands identified during this work suggest that the "ligandin" properties of TvGSTOs play a role in detoxifying wood degradation products
Sutra, Elsa. "Ionophores phosphorés neutres et déprotonables : synthèse, étude physico-chimique et recherche d'activité antibactérienne." Toulouse 3, 2002. http://www.theses.fr/2002TOU30219.
Debernardi, Justine. "Le récepteur Gb3/CD77 : analyse de l’apoptose induite par la vérotoxine-1 dans les cellules de lymphome de Burkitt et recherche de ligands endogènes." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS254.
The Gb3/CD77 glycolipid, which is strongly expressed in Burkitt's lymphoma (BL) cells, is a receptor for the bacterial toxin Verotoxin-1 (VT-1). Previously, our group has shown that VT-1 induces an apoptotic pathway in BL cells which is dependent on caspases and mitochondria. Here, we provide new insights into this pathway. A pro-apoptotic member in the Bcl-2 family, Bid is cleaved by caspase-8 and its truncated form t-Bid is translocated to mitochondria. Using LB cell clones where Bid was inhibited prior to being reexpressed as a non-cleavable mutated form (BID D59A) and a caspase-8 inhibitor to explore VT-1-induced apoptosis, we showed that 1) the full length Bid (FL-Bid) controls the activation of pro-apoptotic proteins Bax and Bak; 2) Both t-Bid and FL-Bid are involved in the release of pro-apoptotic proteins (cytochrome c and Smac/DIABLO) from the mitochondrial intermembrane space to the cytosol; 3) FL-Bid controls the homo-oligomerization of both Bax and Bak, likely contributing to the initial release of cytochrome c and Smac/DIABLO while t-Bid is needed for their hetero-oligomerization followed by amplification of the release. Together, these results reveal a functional cooperation between Bax and Bak during VT-1-induced apoptosis and, most importantly, that activation of caspase-8 and t-Bid is not required to induce the onset of cell death. Gb3/CD77 is also expressed in a proportion of normal B-lymphocytes where it constitutes a differentiation marker but whose function remains uncharacterized. In an effort to look for physiological ligands, we have used a biochemical approach followed by mass spectrometry analysis. Two proteins have been identified as potentially Gb3/CD77 partners, namely galectin-7 and protein S100A11
Abouwarda, Ahmed. "Recherche et étude des gènes de glycosyl-transférases impliqués dans la biosynthèse de constituants de l'enveloppe mycobactérienne." Toulouse 3, 2005. http://www.theses.fr/2005TOU30064.
The prevalence of infection by Mycobacterium tuberculosis is partly due to the ability of the bacillus to persist for years within its cellular target, the human macrophage. The first step of the cellular infection involves the phagocytosis of the bacterium by an alveolar macrophage. One of the routes of entry is mannose-dependent and is believed to be under the control of the Human Mannose Receptor. In this study we have shown that M. Smegmatis mc2155 has a defect in the mannose-dependent phagocytosis by human macrophage. We also investigated the effects of overproduction of some glycosyl- or mannosyl-transferase genes of M. Tuberculosis on mannose-dependent phagocytosis by macrophage and found that some of them were able to complement the defect of mc2155. This result suggests that these glycosyl- transferase genes could participate in the biosynthesis of the Human Mannose Receptor ligands in mycobacteria
Perrot, Thomas. "Diversité fonctionnelle des systèmes de détoxication chez les champignons lignolytiques." Electronic Thesis or Diss., Université de Lorraine, 2018. http://www.theses.fr/2018LORR0140.
Wood decaying fungi play an important role in the carbon cycle by participating in the recycling of organic matter. In addition to their ability to mineralize lignocellulosic biomass, these organisms have the ability to degrade potentially toxic molecules released during this process. Their detoxification system involves several multigenic families including glutathione transferases. These ubiquitous enzymes are grouped into several classes in the fungal kingdom, some of them are widespread in these fungi. In this context, the main objective of this thesis was to understand the functions of glutathione transferases of the Omega class (GSTOs) extended in Trametes versicolor, a white rot fungus. A biochemical and structural approach was led using nine recombinant proteins. Firstly, enzymatic characterization of these isoforms was performed using synthetic substrates, the obtained results demonstrating a similarity of catalytic properties. Then, using a library of pure molecules and another one of complex mixtures from different forest species, a high throughput screening method was applied to identify potential ligands for these enzymes. The resolution of the three-dimensional structure of three isoforms demonstrated the homodimeric state of these proteins and the involvement of two binding sites in the recognition of these ligands: the H site (present in each monomer) and the L site (at the dimer interface). For example, the isoform TvGSTO3S is able to bind several hydroxybenzophenones in its H site, but also a flavonoid, dihydrowogonin. In this case, this interaction with a natural ligand derived from wild-cherry tree extract was demonstrated by an affinity crystallography approach. On the other hand, co-crystallization experiments detected two molecules of another flavonoid, naringenin, in the L site of the isoform TvGSTO6S. Finally, a specific interaction involving the H and L sites of the isoform TvGSTO2S was demonstrated with oxyresveratrol. Structural analysis revealed that the presence of both configurations of the stilbene in the protein: the trans configuration in the H site and the cis configuration in the L site. Thus, despite partial functional redundancy, this research demonstrated the existence of a specific pattern of interactions for each tested isoform. The expansion of the Omega class could indicate that these enzymes are involved in the adaptation of the fungus in its environment. Indeed, the ligands identified during this work suggest that the "ligandin" properties of TvGSTOs play a role in detoxifying wood degradation products
Malicorne, Sébastien. "Recherche d’interactants du domaine immunosuppresseur des protéines d’enveloppe rétrovirales." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS579.
Most viruses have developed mechanisms of resistance or suppression of the immune system to achieve lasting infection of their host. These mechanisms are still imperfectly known. An immunosuppressive (IS) domain has been identified in the transmembrane region of envelope proteins of endogenous or infectious retroviruses. This highly conserved domain has been described, for example, as inhibiting lymphocyte activation. In the laboratory, it has been characterized by tumor cell rejection experiments in vivo, which has made it possible to define inactivating mutations. In order to better understand the mechanisms of resistance of retroviruses to the immune system, my thesis focused on the identification of the protein(s) interacting with the IS domain. Several cellular and molecular approaches have been developed, based for the most part on the use of fluorescent probes obtained by chemical synthesis, consisting of IS domains from different retroviruses. At first, immune system cells that bind viral proteins have been identified: B cells and myeloid cells (monocytes, dendritic cells and macrophages). In a second step, co-immunoprecipitation and affinity chromatography coupled to mass spectrometry were performed to identify on these cells the membrane proteins responsible for these bonds. Several chemical coupling agents have been used to prevent detachment of low affinity binding between proteins and the IS domain. Due to non-reproducible results obtained during these experiments, IS domain binding assays on cells transfected with cDNA libraries, or in double hybrid experiments were performed. These two approaches made it possible to identify membrane proteins potentially involved in the binding of the IS domain: the X1 and X2 proteins. Co-transfections of IS domain and X2 expression vectors demonstrated protein interactions in co-immunoprecipitation and confocal microscopy experiments, particularly with the IS domain of the HIV-1 retrovirus. Concerning X1, its transfection induces binding of the IS domains of HERV-W and MLV on cells membrane. On the other hand, no direct interaction between X1 and the IS domain could be demonstrated, especially in co-immunoprecipitation and confocal microscopy experiments.The discovery of membrane proteins that interact with the IS domain remains a critical issue for understanding the signaling and transcription pathways that allow retroviruses to exert their effect on the immune system, the aim of this work being to identify new therapeutic targets.In conclusion, although further work is still needed, the X1 and X2 proteins may contribute to retroviral immunosuppression
Poulard, Cyril. "Ligands cyclopentadiényles fonctionnalisés : utilisation en série du tantalocène et accès à des structures hétérobimétalliquesComplexes (arène)chrome tricarbonyle optiquement actifs : recherche et mise en œuvre de différentes stratégies de synthèse." Dijon, 2001. http://www.theses.fr/2001DIJOS035.
Sylvestre-Gonon, Elodie. "Caractérisation biochimique et structurale de quelques glutathion transférases de la classe Tau d'arabette (Arabidopsis thaliana) et de peuplier (Populus trichocarpa)." Electronic Thesis or Diss., Université de Lorraine, 2020. http://www.theses.fr/2020LORR0253.
Glutathione transferases (GSTs) constitute a ubiquitous multigene superfamily of enzymes involved in xenobiotic detoxification and secondary metabolism. Canonical GSTs consist of an N-terminal thioredoxin domain and a α-helical C-terminal domain. In terrestrial plants, GSTs can be grouped in 14 classes but also according to the conserved residue found in their catalytic site either cysteine (Cys-GSTs) or serine (Ser-GSTs) GSTs. Ser-GSTs exhibit reduction of peroxides and/or glutathione (GSH) conjugation activities while Cys-GSTs rather exhibit deglutathionylation and dehydroascorbate reductase activities. Some of them also appear to have non-catalytic ligandin properties for the transport or storage of various molecules. The plant-specific Tau GST (GSTU) class is usually the most expanded one. The GSTUs are often over-expressed during biotic and abiotic stresses contributing notably to herbicide detoxification. However, the physiological role of most GSTUs is still poorly documented in planta. By combining phylogenetic, biochemical and structural approaches, this work led to the characterisation of nine GSTUs from Arabidopsis thaliana (AtGSTUs) and six GSTUs from Populus trichocarpa (PtGSTUs). Phylogenetic analysis of the Ser-GSTs present in photosynthetic organisms revealed that the expansion of GSTUs occurred concomitantly with the appearance of vasculature in plants, although some mosses and bryophytes possess GSTUs. Within an organism, GSTUs can be classified into distinct groups according to their catalytic motif. Enzymatic tests using recombinant proteins showed that almost all studied GSTUs exhibit GSH conjugation and peroxide reduction activities against different model substrates (CDNB, isothiocyanate derivatives, hydroperoxides). The three-dimensional structures of two GSTUs have been resolved and these adopt the classical canonical GST fold with some notable difference between them. The biochemical and structural analyses of these AtGSTUs and PtGSTUs further showed that some of them bind bacterial porphyrins while others bind polyphenolic compounds. Among the enzyme-ligand complexes identified, the structure of a bacalein-GSTU has been solved. The use of metabolites enriched samples extracted from A. thaliana and P. trichocarpa is the next step to decipher the role of GSTUs in planta
Lecerf, Schmidt Florine. "Conception et développement de nouveaux ligands des transporteurs ABCG2 et MRP1 dans le cadre de la résistance à de multiples drogues anticancéreuses." Thesis, Université Grenoble Alpes (ComUE), 2015. http://www.theses.fr/2015GREAV012/document.
Resistance to chemotherapeutic agents (Multidrug Resistance or MDR) is a major hurdle for anticancer chemotherapy. Among different mechanisms involved in MDR, the overexpression of membrane proteins belonging to ABC family is the most relevant one. Among such proteins, ABCG2 and MRP1 are considered to play an important role. These transporters are able to induce a massive efflux of anticancer agents out of the cancer cells, reducing their intracellular concentration and their therapeutic potency. In order to overcome this resistance, novel modulators of ABCG2 and MRP1 were designed, synthetized and tested biologically. In this context, new derivatives of chromones as inhibitors of ABCG2 were developed in order to restore sensitivity of cancer cells to chemotherapeutic agents. In addition, molecular modelling of new pharmacophores allowed us to gather new data exploring ABCG2-ligand interactions. New modulators of MRP1, derivatives of flavonoids, are able to induce a massive efflux of intracellular glutathione that is mediated by the protein, without being transported and causing selective apoptosis of cancer cells overexpressing MRP1
Wang, Rong Fu. "Mise au point et évaluation d'un nouveau radioligand iodé spécifique pour l'imagerie tomoscintigraphique des neurorécepteurs aux opioi͏̈des." Toulouse 3, 1995. http://www.theses.fr/1995TOU30094.
Benoît, Vincent. "Recherche de descripteurs spécifiques d'interactions protéine-protéine et protéine-ligand." Paris 6, 2006. http://www.theses.fr/2006PA066235.
Understanding the determinants of specific protein-protein and protein-ligand interactions is of great interest for both fundamental as well as applied research. The major part of this work concerned protein-protein interfaces characterization. Noteworthy is that information for generating reliable protein-protein complex datasets is not directly accessible from PDB structures. Also, interfaces involving crystallographic symmetric chains are not directly reachable. Thus creating a database giving access to multiple protein-protein and crystallographic interfaces was found to be worthwhile. Cross referencing multiple databases as well as computing all possible interfaces inside a crystal allowed us to create a fast and flexible tool. Moreover we used docking tools to investigate protein-ligand interactions. Structures of validated inhibitors of Proliferating Cell Nuclear Antigen (PCNA) polymerase delta interaction were given to us through collaboration with the Curie Institute at Orsay. Apart from generating putative structures of PCNA-inhibitors complexes we investigated docking sites locations of validated inhibitors versus putative locations of non inhibitor ones
Cheve, Gwénaël. "Recherches en serie indolique : derives antioxydants et ligands des recepteurs melatoninergiques (doctorat : pharmacochimie)." Lille 2, 2000. http://www.theses.fr/2000LIL2P264.
Thorin, Savarit Chantal. "Estimation des paramètres pharmacologiques dans les modèles d'interactions ligand-récepteur." Nantes, 2010. https://archive.bu.univ-nantes.fr/pollux/show/show?id=dcd2d038-5c6a-40bf-a641-d363db9727cb.
Amrane, Samir. "Analyse des répétitions de trinucléotides impliquées dans des pathologies neurodégénératives et recherches de ligands spécifiques." Paris 6, 2006. http://www.theses.fr/2006PA066333.
Trinucleotide repeats are involved in a number of debilitating diseases such as myotonic dystrophy, Huntington disease and fragile X syndrome. 12 to 75 base-long (CXG)n N=A,T,C,G oligodeoxynucleotides were analysed using a combination of biophysical (UV-absorbance, CD, differential scanning calorimetry) and biochemical methods (non denaturing gel electrophoresis, enzymatic footprinting). All oligomers formed intramolecular structures with a melting temperature which was only weakly dependent on oligomer length. All sequences form stable structures at 37°C under near physiological conditions. Thermodynamic analysis of the denaturation process by UV-melting and calorimetric experiments revealed a surprising length-dependent discrepancy between the enthalpy values deduced from model-dependent (UV-melting) and model-independent experiments (calorimetry). Such behavior is analyzed in the framework of a brocken-hairpin model, in which long CXG oligomers do not fold into a simple long hairpin-stem intramolecular structure, but allow the formation of several independent folding units of unequal stability. We have also shown that small ligands derived from acridine binds to these structures with a good affinity and specificity
Hermann, Patrice. "Recherche du ligand du CD40 : étude du rôle de son interaction avec le CD40 dans la réponse lymphocytaire B." Lyon 1, 1995. http://www.theses.fr/1995LYO1T120.
Wang, Shiwei. "La recherche expérimentale de la neurorrhaphie chirurgicale et des thérapies moléculaires pour les lésions du nerf périphérique." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS575.
Peripheral nerve injury (PNI) results from multiple causes, including trauma, inflammation, ischemia and tumor compression. Dysfunction of affected muscles and sensory deprivation caused by PNI result in huge obstacles for suffering patients and their families. Even though many achievements for PNI treatment have been realized during the last decades, poor clinical prognosis remains a challenge for researchers and clinicians. This prompted me to explore new approaches for nerve repair by using two different types of nerve grafts associated with several nerve injuries of donor nerve, but also investigate the therapeutic potential of several small molecules including neurosteroids, TSPO agonist ligands and potassium channel activators for promoting neuroprotection and neuroregeneration. My thesis is divided into two parts and makes use of two experimental rat models. The major aims were : 1) To determine the optimal injury condition of a donor nerve for end-to-side neurorrhaphy by using a sciatic end-to-side neurorrhaphy model with different types of autologous nerve grafts (fresh or predegenerated). Neuronal retrograde labeling, analysis of myelinated axons and the evaluation of action potentials were performed to evaluate neuroprotection and neuroregeneration. This approach showed that effective axonal regeneration into a nerve graft occurred only when axonal resources supplied by the donor nerve reached 50% of its total number of axons. In addition, the use of a predegenerated nerve graft was beneficial for neuroregeneration by improving the environment of the nerve pathway. 2) To investigate the efficacy of the administration of small molecules including progesterone, Nestorone, etifoxine and Kv7.2/7.3 channel activators for neuroprotection, axonal regeneration and functional recovery. For these studies, we developed a cervical spinal nerve crush injury model. The same histological analysis mentioned above, measures of evoked potentials and motor or sensory behavioral tests were performed to evaluate neuroprotection, neuroregeneration and functional recovery. Progesterone and Nestorone showed benefits on neuroprotection at early stages and on neuroregeneration and functional recovery at later stages after nerve injury. Interestingly, the mono-therapy of etifoxine promoted motor functional recovery while the mono-therapy of GRT12 was beneficial for sensory functional recovery. The synthetic compounds combining TSPO ligand and Kv7.2/7.3 channel activator properties promoted both motor and sensory functional recovery. In conclusion, our study revealed that 50% axotomy of a donor nerve in the end-to-side neurorrhaphy paradigm is the optimal condition for neuroregeneration. We also verified the advantage of using predegenerated instead of a fresh nerve graft to improve the regenerative environment. We also demonstrated the effectiveness of progesterone and Nestorone in neuroprotection and neuroregeneration, and that new synthetic compounds with TSPO ligand and Kv7.2/7.3 channel activator properties promoted motor and sensory recovery
Seghrouchni, Samira. "Recherches dans la série des tétraazaporphyrinogènes : modifications structurales et étude dynamique : RMN des complexes de ruthénium (II)." Montpellier 2, 1993. http://www.theses.fr/1993MON20011.
Genevois, Anne-Laure. "Implication du récepteur à dépendance TRKC et de son ligand NT-3 en cancérogénèse : de la recherche fondamentale à la thérapeutique." Phd thesis, Université Claude Bernard - Lyon I, 2013. http://tel.archives-ouvertes.fr/tel-01067136.
Pons, Julien. "Caractérisation structurale du mode de liaison à la protéine β-TrCP, première étape vers la recherche d'inhibiteurs de NF-kappaB". Paris 6, 2008. http://www.theses.fr/2008PA066355.
Paul, Nicodème. "Développement de nouvelles applications en criblage virtuel." Strasbourg 1, 2003. http://www.theses.fr/2003STR13193.
Based on molecular docking, virtual screening or in silico screening becomes of increasing interest in the pharmaceutical industry. In this study, we propose ConsDock a consensus docking program that takes advantage of three widely used docking tools Dock, Gold and FlexX. ConsDock significantly outperforms single docking with respect to the docking accuracy of the top-ranked pose. Then, for inverse screening purpose, we develop a protein database based on the Protein data Bank (sc-PDB). This database has been used to recover target of known ligands by using an in-house inverse screening process based on Gold. At last, as we were interested in developing activated models of G Protein-Coupled Receptors or GPCRs, we present a simulation process of ligand-based GPCR folding. The simulation is performed by genetic algorithms. By using a GPCR and a ligand, the algorithm tries to find stable conformations of GPCR by rotating and translating helices. Movement is performed according experimental observations. We tested the method on the X-ray structure of rhodopsin complexed with the cis-retinal. We got some good results when used specific genetic operators for a sufficient number of generations
Malbert-Colas, Laurence. "Recherche et identification de partenaires du canal épithélial à sodium ENaC : étude du rôle potentiel de ces partenaires dans la régulation de l'activité de ENaC." Paris 7, 2003. http://www.theses.fr/2003PA077168.
Boisson, Jean-Charles. "Modélisation et résolution par métaheuristiques coopératives : de l'atome à la séquence protéique." Electronic Thesis or Diss., Lille 1, 2008. http://www.theses.fr/2008LIL10154.
Ln this thesis, we show the importance of the modeling and the cooperation of metaheuristics for solving real problems in Bioinformatics. Two problems are studied: the first in the Proteomics domain for the protein identification from spectral data analysis and the second in the domain of the structural analysis of molecules for the flexible molecular docking problem. So, for the first problem, a new model has been designed based on a direct comparison of a raw experimental spectrum with protein from databases. This model has been included in an identification engine by peptide mass fingerprinting called ASCQ_ME. From this model, an approach for the de novo protein sequencing problem has been proposed and validated. ln this problem, a protein sequence has to be found with only spectral information. Our model is a three step approach called SSO for Sequence, Shape and Order. After a study of each step, SSO has been implemented and tested with three metaheuristics collaborating sequentially. For the second problem, a study of new multi-objective models has been made and has allowed to design eight different models tested with parallel multi-objective genetic algorithms. Twelve configurations of genetic operators has been tested in order to prove the efficiency of the hybridizing of genetic algorithms with local searches. For each part of this work, the ParadisEO platform has been used and more particularly the ParadisEO-MO part dedicated to single solution based metaheuristics for which we have substantially contributed. All this work has been funded by the "PPF Bio-Informatique" of the "Université des Sciences et Technologies de Lille" and by the ANR Dock project
Boisson, Jean-Charles. "Modélisation et résolution par métaheuristiques coopératives : de l'atome à la séquence protéique." Phd thesis, Lille 1, 2008. http://tel.archives-ouvertes.fr/tel-00842054.