Teses / dissertações sobre o tema "Recherche de ligands/substrats"
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Perrot, Thomas. "Diversité fonctionnelle des systèmes de détoxication chez les champignons lignolytiques". Thesis, Université de Lorraine, 2018. http://www.theses.fr/2018LORR0140/document.
Texto completo da fonteWood 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
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.
Texto completo da fonteWood 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
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.
Texto completo da fonteGlutathione 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
El, khoury Takla. "Recherche des substrats et des activateurs d'une nouvelle famille de protéine kinase bactérienne". Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAV003.
Texto completo da fonteProtein kinases are responsible of protein phosphorylation, a post-translational modification and a very effective and almost instantaneous control of a multitude of cellular processes. They are involved in the regulation of metabolic pathways in living organisms enabling their adaptation to environmental changes. In prokaryotes, the existence of serine/threonine and tyrosine kinases was, for a long time, a subject of controversy. However, over the past two decades, many studies have shown that these types of phosphorylation (Ser/Thr/Tyr) do exist in bacteria and are involved in the regulation of a wide variety of biological processes. In addition to protein kinases related to eukaryotic enzymes, bacteria also have some specific protein kinases having no structural resemblance to their eukaryotic homologues which, if essential, made them a possible target for new antimicrobial agents. YdiB is a novel bacterial protein kinase from Bacillus subtilis. In situ localisation of YdiB has been studied by immunofluorescence which reveals its presence near the plasma membrane. The interaction of YdiB with the membrane phospholipids was assessed by flotation assay and surface plasmon resonance demonstrating the presence of a stable and strong interaction between the kinase and two phospholipids: phosphatidylserine and phosphatidylethanolamine. In addition, the affinity constant (KD) between YdiB and phosphatidylserine was found to be equal to 13.3 x 10-9 M. Moreover, these two phospholipids or just their charged headgroups were able to significantly induce the autophosphorylation of YdiB.On the other hand, the role of YdiB in the bacterial growth especially under oxidative stress was also studied in the wild-type strain and in ∆ydiB mutant. Under oxidative stress conditions, the deleted strain was unable to survive whereas a conditional complementation of ∆ydiB mutant was able to restore a normal growth profile for the bacterium. This reveals the important role played by YdiB in the bacterial resistance to oxidative stress. In addition, protein involved in the resistance to oxidative stress like Superoxide dismutase F (SodF) and superoxide dismutase A (Sod A) were tested as potential substrates for YdiB. Doing the trans-phosphorylation assay, we were able to prove that Sod B could be a potential substrate for YdiB thus explaining its involvement in the resistance to oxidative stress in Bacillus subtilis
Maitro, Guillaume. "Etude de dérivés soufrés en tant que substrats ou ligands en catalyse au palladium". Paris 6, 2007. http://www.theses.fr/2007PA066041.
Texto completo da fonteDagher, 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.
Texto completo da fonteLe, Manach Claire. "Recherche de ligands du système tubuline/microtubules par chimie combinatoire dynamique". Paris 11, 2008. http://www.theses.fr/2008PA112340.
Texto completo da fonteThe 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
Dillard, Pierre. "Impact de la présentation des ligands sur la biophysique de l’adhésion des lymphocytes T". Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4085/document.
Texto completo da fonteT- cells play a central role in cell mediated adaptive immune response. They are a class of lymphocytes that carry distinctive receptors - the TCRs (T cell receptor), which are responsible for specific recognition of foreign peptides in the body. Molecular interactions between the TCR complex and its ligand is followed by cell adhesion and spreading accompanied by dramatic changes at molecular and cellular scale. In this thesis we focus on the events that immediately follow recognition. I report a systematic study of the spreading dynamics and morphology (in terms of adhesion area and actin organization) of T lymphocytes on substrates with mobile or immobilized anti-CD3 (a ligand targeting the TCR complex). The spreading behaviour is seen to be dramatically different on the two types of substrates. Interestingly, on blocking myosin-II or by inclusion of ICAM (ligand of LFA1 integrins) on the substrate, these differences tend to disappear. We propose a model, partially inspired by earlier models of neuronal growth cones and filopodia, that links the dynamics of the leading edge of the spreading T cell to the friction generated at the surface by dragging or pinning of the ligands. I also report studies on T cells interacting with substrates decorated with nano-scale islands of anti-CD3 in a sea of repulsive PEG or a supported lipid bilayer. Dramatic differences in adhesion, organization of actin, and receptor distribution are observed on different geometries. I report advances in multi channel RICM towards the reconstruction of not only the topography of the proximal membrane of the T cell with high level of confidence but also the distal surface of lamellipodia
Capon, Jean-François. "Réactivité de substrats insaturés (alcynes, enynes, ions carbenium, allenylidenes) coordinés à des entités binucléaires du molybdène". Brest, 1995. http://www.theses.fr/1995BRES2002.
Texto completo da fonteVillalobos, Oliver Susana Patricia. "Approches expérimentales et théoriques du comportement dynamique de cycles de substrats binaires". Compiègne, 1990. http://www.theses.fr/1990COMPD301.
Texto completo da fonteMossand, 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.
Texto completo da fonteThe 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
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.
Texto completo da fonteDagher, 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.
Texto completo da fonteDARDE-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.
Texto completo da fonteLawson, 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.
Texto completo da fonteAs 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.
Texto completo da fonteLafite, Pierre. "ETUDE du CYTOCHROME P450 2J2 HUMAIN :Recherche de substrats et d'inhibiteurs sélectifs ;Détermination de la topologie de son site actif". Phd thesis, Université René Descartes - Paris V, 2007. http://tel.archives-ouvertes.fr/tel-00192090.
Texto completo da fonteBraconnier, Agnès. "Recherche de Clostridium botulinum dans des plats cuisinés et étude de sa croissance dans des substrats à base de légumes". Aix-Marseille 3, 2001. http://www.theses.fr/2001AIX30062.
Texto completo da fonteThis work is a contribution to a risk assessment of C. Botulinum in cooked chilled foods containing vegetables. A molecular method was used for the detection of C botulinum spores in commercial cooked chilled food and their raw material. This method use degenerated primers for PCR amplification of a 260-bp fragment common to type A, B E F and G neurotoxm genes, and molecular probes specifics to type A, B and E neurotoxin genes (Fach et al. 1995). After sample enrichment, this method allowed the detection of 1 to 10 spores of C. Botulinum per g. All samples tested for the presence of type A, B and E C. Botulinum were negative, suggesting that the prevalence of C. Botulinum in food containing vegetables is lower than 1-10 spores/g. Growth of several proteolytic C botulmum strains was studied in cooked vegetable-based media. Probabilities of growth at 10 C and 12 ʿC of proteolytic C. Botulinum spores in vegetables are low. .
Diab, Lisa. "Réaction d’alkoxycarbonylation catalysée par des complexes du palladium : étude de la régio- et stéréosélectivité : utilisation de ligands chiraux et/ou de substrats chiraux". Toulouse 3, 2007. http://www.theses.fr/2007TOU30313.
Texto completo da fonteSavarin, 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.
Texto completo da fontePoncet-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.
Texto completo da fonteThe 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)
Khaled, Amira. "Recherche de nouveaux substrats donneurs pour les glycosyltransférases : modifications au niveau de la base nucléotidique et mime de la liaison diphosphate". Paris 11, 2005. http://www.theses.fr/2005PA112066.
Texto completo da fonteThe availability of cloned glycosyltransferases has made enzymatic glycosylation a realistic alternative to chemical synthesis. However, a severe drawback to this approach is the requirement for sugar nucleotides. Donor substrates with a simpler structure than sugar nucleotides, prepared at a lower cost, would be highly desirable. We first looked at the possible changes of the nucleotide base. Thus we prepared four unnatural sugar nucleotides UDP-Fuc, ADP-Fuc, CDP-Fuc and a derived from cyanuric acid, NDP-Fuc, analogues to the natural fucose donor GDP-Fuc. These analogues were tested toward a recombinant human α(1-3/4)fucosyltransferase (Fuc TIll). Efficiency of the four analogues towards FucT-lll was in the following order: UDP-Fuc = ADP-Fuc > NDP-Fuc > CDP-Fuc. Accordingly, the unnatural sugar nucleotide, analogue to the natural N-acetylglucosamine donor UDP-GlcNAc was prepared, and tested as a glucosaminyl donor towards Neisseria meningitidts N-acetylglucosaminyl transferase (LgtA), ADP-GlcNAc was recognised with 0. 1% efficiency as compared with UDP-GlcNAc, the natural donor substrate. Furthermore, we have synthesized two analogues of UDP-GlcNAc and GDP-Fuc in which the diphosphate bond was replaced by a carbonylaminosulfonyl group: the glucosaminyl-derivative obtained turned out not to be a donor substrate. It showed no inhibition when tested as an inhibitor for LgtA. The fucosyl-derivative obtained as a µβ mixture was evaluated as a substrate for Fuc TIll in the presence of Mn2+ and Yb3+. No conversion was observed in the both cases. Inhibition of the enzyme by a anomer is suspected and it should be interesting to evaluate the pure β compound
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.
Texto completo da fonteAza 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
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.
Texto completo da fonteLubatti, Frédéric. "Synthèse de nouveaux ligands organophosphorés chiraux mixtes de type P/N. Applications dans des réactions de substitution nucléophiles asymétriques sur substrats allyliques catalysées par des complexes du palladium (0)". Aix-Marseille 3, 1999. http://www.theses.fr/1999AIX30091.
Texto completo da fonteDodi, 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.
Texto completo da fonteOrganic 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
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.
Texto completo da fonteFournier, 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.
Texto completo da fonteOlivieri, 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.
Texto completo da fonteFKBP12 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
Smet-Nocca, Caroline. "Etude des interactions entre la peptidyl-prolyl cis/trans isomérase Pin1 et la protéine microtubulaire Tau. Recherche d'inhibiteurs ciblant la liaison de Pin1 à ses substrats phosphorylés". Phd thesis, Université du Droit et de la Santé - Lille II, 2004. http://tel.archives-ouvertes.fr/tel-00354986.
Texto completo da fonteNous avons ciblé les interactions entre Pin1 et la protéine Tau comme modèle de substrats pour une étude détaillée des mécanismes intervenant à l'échelle moléculaire, sur base de substrats peptidiques, qui permettraient d'expliquer le rôle fonctionnel de Pin1. L'interaction avec les substrats au travers des motifs Ser/Thr-Pro phosphorylés est double : un domaine de liaison WW permet la liaison du substrat et un domaine catalytique PPIase (peptidyl-prolyl isomérase) catalyse l'isomérisation cis/trans des prolines. Un criblage par RMN des différents motifs phospho-Ser/Thr-Pro au sein de la protéine Tau a permis de déterminer un nouveau site d'interaction centré autour du motif Thr212-Pro213, phosphorylé uniquement dans la forme pathologique de Tau.
Nous avons étendu l'investigation des interactions avec Pin1 à l'échelle de la protéine Tau entière. Comme pour la plupart des régions protéiques impliquées dans les interactions avec Pin1, la protéine Tau se caractérise par une absence de structure globale qui limite considérablement les études par RMN. Un fragment peptidique de 40 acides aminés comprenant les sites Thr231 et Thr212 phosphorylés a permis de montrer un rôle régulateur du domaine WW dans l'activité enzymatique. Une première étude avec une protéine mutante mimant l'état phosphorylé de Tau a montré une interaction avec le domaine catalytique de Pin1 et a nécessité la mise au point préalable d'une technique d'attribution de la protéine Tau par RMN que nous avons appelé « mapping peptidique ».
La phosphorylation du domaine WW de Pin1 est associée à l'inhibition de la liaison des substrats et joue un rôle dans la régulation de l'activité de Pin1 in vivo. La forme non phosphorylée active de Pin1 est retrouvée majoritairement dans les cellules cancéreuses et la forme phosphorylée inactive dans les cellules saines. Nous avons envisagé de cibler les interactions entre Pin1 et les phospho-peptides avec la synthèse de molécules organiques mimant le dipeptide phosphoThr-Pro et la mise en œuvre d'un test de criblage par RMN pour l'obtention d'inhibiteurs ciblant le domaine WW de Pin1 qui pourraient mimer la forme inactive de la protéine.
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.
Texto completo da fonteDaval, 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.
Texto completo da fonteMuscarinic 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
Pégeot, Henri. "Étude des gluthation transférases de la classe Phi du peuplier (Populus trichocarpa) : caractérisation structurale, enzymatique et recherche de molécules cibles". Thesis, Université de Lorraine, 2015. http://www.theses.fr/2015LORR0242/document.
Texto completo da fonteGlutathione transferases (GSTs) belong to a multigenic family whose presence in most eukaryotes, prokaryotes and archaea reflects their widespread nature and very likely important functions. These enzymes represent a major group of enzymes involved in xenobiotic detoxification and secondary metabolism. From the most recent genomic and phylogenetic analyses, the GST family is subdivided into 14 classes that can be separated into two main groups based on the catalytic residue which is either a serine (Ser-GST) or a cysteine (Cys-GST). Ser-GSTs usually catalyze glutathione (GSH) conjugation and/or peroxide reduction. On the other hand, Cys-GSTs cannot perform GSH-conjugation reactions but instead catalyze thiol-transferase, dehydroascorbate reductase and deglutathionylation reactions. Ser-GSTs from the Phi class (GSTF) are present in photosynthetic organisms and some basidiomycetes. This class is composed of a large number of genes compared to other GST classes which are amongst the most stress-inducible. The corresponding proteins have been extensively studied in crops with regard to their detoxification activities toward herbicides. However, with a few exceptions, very little is known about their roles in planta and it is not well understood why this class has expanded. By combining molecular, cellular, biochemical and structural approaches, the eight isoforms from the model tree Populus trichocarpa have been characterized during this PhD project. Phylogenetic analysis of GSTFs in the green lineage shows that the apparition of this class is concomitant with the appearance of terrestrial plants and that different groups can be distinguished based on the active site signature. RT-PCR analysis of the eight isoforms of GSTFs showed that transcripts mostly accumulate in female flowers, petioles and fruits. Some aspects of the reaction mechanism have been characterized by determining kinetic parameters of the eight poplar GSTFs and of several mutated variants for key residues towards model substrates. The structures of five GSTFs have been solved and these dimeric proteins display a typical GST fold but specificities have been observed at the catalytic site level. Moreover, considering the demonstrated capacity of GSTF orthologs to bind hormones, anthocyanins or flavonoids, and the consistent high expression of poplar GSTFs in female flowers and fruits, two organs rich in these molecules, we speculate that they may also possess ligandin properties. Preliminary results have been obtained regarding the nature of the substrates in various poplar organs by analyzing protein thermostability in the presence of putative ligands. In order to assess whether a functional redundancy between poplar Phi GSTs exists and to identify their mode of action (catalytic vs ligandin functions), we started to isolate and identify physiological substrates
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.
Texto completo da fonteDebernardi, 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.
Texto completo da fonteThe 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
Sutra, Elsa. "Ionophores phosphorés neutres et déprotonables : synthèse, étude physico-chimique et recherche d'activité antibactérienne". Toulouse 3, 2002. http://www.theses.fr/2002TOU30219.
Texto completo da fonteCholley-Vignardet, Céline. "Approche de la connaissance d'une nouvelle keratinase de doratomyces microsporus (sacc. ) morton et smith par des etudes physico-chimiques et la recherche d'applications sur differents substrats keratinises (doctorat : sciences pharmaceutiques)". Besançon, 1999. http://www.theses.fr/1999BESA3511.
Texto completo da fonteBenmansour, Saloua. "Etude des caractéristiques de la liaison des inhibiteurs et des substrats au complexe de capture neuronale de la dopamine à l'aide d'un ligand marque spécifique le 3H GBR 12783". Rouen, 1989. http://www.theses.fr/1989ROUES053.
Texto completo da fonteAbouwarda, 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.
Texto completo da fonteThe 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
Costas, Salgueiro Miquel. "Activació d'O2, HOOH i t-BuOOH amb complexos de Cu i Fe amb lligands N-heterocíclics aromàtics i macrocíclics per l'oxidació de substrats orgànics i inorgànics en condicions suaus". Doctoral thesis, Universitat de Girona, 1999. http://hdl.handle.net/10803/96659.
Texto completo da fonteTesis organitzada en set capítols independents: I) activació d’O2, HOOH i t-BuOOH amb complexos de Cu i Fe per a l’oxidació de substrats orgànics i inorgànics; II) activació de dioxigen catalitzada per Cu(I) per a l’oxidació de substrats orgànics amb condicions suaus; III) la funcionalització d’hidrocarburs saturats. Noves evidències del paper de l’enllaç Fe-C en Química Gif; IV) transformació d’amines aromàtiques amb HOOH catalitzada amb Fepy4CI2+; V) mecanisme de reacció de LCu(I)CIO4, L = tris[(3-t-butil)-piridil] amina, amb oxigen en acetona; VI) complexos dinuclears de Cu i Zn amb lligands hexaazamacrocíclics
Malicorne, Sébastien. "Recherche d’interactants du domaine immunosuppresseur des protéines d’enveloppe rétrovirales". Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS579.
Texto completo da fonteMost 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.
Texto completo da fonteLecerf, 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.
Texto completo da fonteResistance 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.
Texto completo da fonteBoisson, 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.
Texto completo da fonteLn 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.
Texto completo da fonte