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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
131

Structures hélicoïdales d'hligomères dirigées par un béta-Amino acide bicyclique / Helical Structure of Oligomers Promoted by a Bicyclic beta-Amino Acid

André, Christophe 03 July 2012 (has links)
Ce travail de thèse est consacré à la synthèse et la caractérisation structurale par spectroscopies RMN, IR, CD et RX de nouveaux oligomères non naturels qui s'inscrivent dans la famille des foldamères. Ils sont construits en particulier à partir d'un β-aminoacide bicyclique chiral original: l'acide (S)- ou (R)-aminobicyclo[2.2.2]octane-2-carboxylique ((S)- et (R) ABOC) que nous avons développé. Ce motif est issu d'une synthèse stéréocontrollée, dont l'étape clef est une réaction de Diels-Alder asymétrique. Après avoir montré que ce motif est un mime de coude peptidique il a été utilisé pour la synthèse de plusieurs séries d'oligomères. Deux grandes familles ont été développées: des oligourées et des oligoamides. A l'intérieur de ces familles, des homo- et des hétéro-oligomères ont été synthétisés et leur préférence conformationnelle a été définie. Les analyses RMN et les études cristallographiques ont permis de montrer qu'en fonction de leur séquence ils sont capables d'adopter plusieurs types d'hélices. Les homo-oligourées d'ABOC et des hétéro-oligourées alternant l'ABOC et des β3-aminoacides ont conduit à des hélices-12/14. Les oligoamides construits par des alternances d'ABOC et de β3-aminoacides dans un rapport 1/1 et des alternances d'ABOC et d'α-aminoacides dans un rapport 1/1 ou 1/2 ont conduit respectivement à des hélices 10/12, 16/18 et 12/14. / This thesis is devoted to the synthesis and FT-IR, CD, NMR and X-ray structural characterization of new unnatural oligomers belonging to the family of foldamers. In particular they are constructed from an original chiral bicyclic β-amino acid: (S)- and (R)-aminobicyclo[2.2.2]octane-2-carboxylic acid ((S) - and (R) ABOC ) that we have developed. This motive was obtained via a stereocontrolled synthesis using an asymmetric Diels-Alder reaction as key step. Firstly, this motive was shown to induce turn in peptide sequence and then it was used for the synthesis of several series of oligomers. Two main families were developed: oligoureas and oligoamides. Within these families, homo-and hetero-oligomers were synthesized and their conformational preferences were defined. NMR analysis and crystallographic studies have shown that depending on their sequence they are able to adopt several types of helices. ABOC homo-oligoureas and hetero-oligoureas containing both ABOC residue and β3-amino acid favor a 12/14-helix. Oligoamides with 1/1 alternation of ABOC and β3-amino acids, and heterogeneous backbones with 1/1 and 1/2 ABOC/α-amino acid residue patterns adopt 10/12-, 16/18- and 12/14-helix, respectively.
132

Efeito da instalação de estacas helicoidais em solo tropical / Effects of installation of helical piles in tropical soils

Santos Filho, João Manoel Sampaio Mathias dos 31 March 2014 (has links)
Neste trabalho e avaliado o comportamento de estacas helicoidais instaladas em solo residual tropical, submetidas a esforços de tração. Para este fim, foram ensaiadas estacas helicoidais em dois campos experimentais distintos, um em Itirapina (SP), e outro em Betim (MG). No primeiro terreno, as hélices das estacas ficaram instaladas em solo residual não saturado, e no segundo terreno em solo residual saturado. Neste tipo de fundação, o efeito da instalação da estaca no solo acima das hélices e um dos fatores que afetam significantemente a capacidade de carga a tração da estaca. Portanto, considerando-se a modificação que ocorre na estrutura de solos residuais tropicais após serem penetrados pelas hélices da estaca durante a sua instalação no terreno, a presente pesquisa foi desenvolvida com o intuito de compreender o efeito desta desestruturação do solo no comportamento da estaca a tração. Para esta avaliação, foi realizado um programa experimental com provas de carga em estacas helicoidais (instrumentadas e não-instrumentadas) e ensaios de laboratório em amostras indeformadas do solo coletado ao redor de uma estaca instalada no terreno de Itirapina. Os resultados mostram o efeito significante da instalação na capacidade de carga a tração deste tipo de estaca, principalmente no caso de solo poroso e não saturado. Alem disso, por meio dos ensaios em estacas instrumentadas, foi verificado que este efeito e mais acentuado no solo acima das hélices superiores, que foi penetrado mais vezes durante a instalação. / In this work, it was evaluated the behavior of helical piles installed in tropical residual soil under tensile loads. For this purpose, helical piles of different configuration were tested in two different experimental sites, one in Itirapina (SP), and another in Betim (MG). In Itirapina, the pile helices were installed in unsaturated residual soil, and in Betim in saturated residual soil. For this type of foundation, the effect of pile installation on the soil above the helices is one of the factors that significantly affect the pile uplift capacity. Therefore, considering the changes that occur in the structure of tropical residual soils after being penetrated by the helices during pile installation, this research was conducted in order to understand the effect of this soil alteration on the uplift behavior of helical piles installed in this type of soil. For this evaluation, pile load tests were carried out on instrumented and non-instrumented helical piles. Also, laboratory tests were performed on undisturbed soil samples collected around a pile installed in the site of Itirapina. The results show the significant effect of pile installation on the uplift capacity of the tested helical piles, especially in the case of porous and unsaturated soil. In addition, through the tests on the instrumented piles, it has been found that this effect is more pronounced in the soil above the upper helices, which were penetrated more times during pile installation.
133

Síntese de polímeros helicoidais para o reconhecimento de moléculas quirais e catálise assimétrica / Synthesis of helical polymers for recognation of chiral molecules and assymetric catalysis

Takata, Leandro Mitsuo Shimura 06 March 2015 (has links)
Os estudos desenvolvidos nessa tese tiveram como objetivo principal o desenvolvimento de materiais que pudessem ser aplicados tanto para o reconhecimento de moléculas quirais quanto para catálise. A estrutura sugerida baseou-se em nanopartículas de ouro funcionalizadas com polímeros helicoidais ligados à superfície do metal através de um átomo de telúrio. O trabalho foi desenvolvido em quatro etapas, consistindo a primeira dos estudos de funcionalização de nanopartículas de ouro com os organoditeluretos, onde foi observado que a presença de diferentes grupos funcionais não interfere no processo. A segunda etapa foi a investigação da tolerância do catalisador de ródio, necessário para a polimerização, à presença do átomo de telúrio. Os resultados mostraram que a atividade do catalisador é inibida na presença do ditelureto, contudo, o mesmo não ocorre quando o composto está ligado à superfície da nanopartícula. A terceira e quarta etapas foram o desenvolvimento de polímeros helicoidais baseados em estruturas poli(fenilacetilênica)s, sendo uma delas desenvolvida no laboratório do Prof. Alcindo Dos Santos (terceira etapa - Brasil) e a outra no laboratório do Prof. Eiji Yashima (quarta etapa - Japão). Nos estudos da terceira etapa foi dado foco a preparação de um polímero que pudesse ser aplicado tanto para o reconhecimento de moléculas quirais quanto para catálise assimétrica, contudo, o material obtido foi bastante insolúvel na maioria dos solventes orgânicos e são necessárias modificações na estrutura do monômero para aumentar a solubilidade do respectivo polímero. Na última etapa foi investigada a influência da estrutura helicoidal em reações assimétricas, sendo preparados copolímeros constituídos por uma unidade quiral sem atividade catalítica e uma unidade aquiral com atividade catalítica. Os resultados mostraram que a unidade aquiral é capaz de promover transformações assimétricas quando presente em uma estrutura helicoidal com um sentido preferencial da hélice Com o trabalho desenvolvido determinou-se que é possível a preparação dos materiais desejados através do crescimento do polímero na superfície da nanopartícula. Preparou-se com sucesso o monômero que deverá ficar ancorado no metal, restando sintetizar um monômero de estrutura adequada para realizar o reconhecimento de moléculas e catálise, como desejado / The studies done in this PhD thesis aimed the preparation of a material that could be used in the recognition of chiral molecules and as catalysts. Its structure was based on gold nanoparticles that was functionalized with helical polymers containing a tellurium atom as an attach point. The presentation of the results was divided in four parts and the first one was the studies about the functionalization of gold nanoparticles with organoditellurides as a model material. It was observed that the presence of various functional groups in organic tellurides does not interfere into the process. The second part was the investigation of the tolerance of the rhodium catalyst, necessary for the polymerization, to the presence of the tellurium atom. The results showed that the activity of the catalyst was inhibited in the presence of a ditelluride, however, the polymerization occured when it was linked in the nanoparticle. The third and fourth parts consisted in the synthesis of the helical polymer based on oly(phenylacetilene)s structure, which one of them was prepared in professor Dos Santos\'s laboratory (third step - Brazil) and the other part in the professor Yashima\'s laboratory (fourth step - Japan). The studies of the third step was the preparation of polymers that could be applied for the recognition of chiral molecules and assymetric catalysis, however, the obtained material was too insoluble in many organic solvents and it is necessary to modify the structure of the monomer to increase the solubility of the respective polymer. In the last step was investigated the influence of the helicity in assymetric reactions. It was prepared copolymers constituted by a chiral unit without any catalytic activity and an achiral unit containing the catalytic functional group. The results showed that the achiral unit was capable to promote assymetric transformation when embebed in a preferred-handed helical structure. In this work was determined that is possible to prepare the suggested materials raising the polymer in the nanoparticle surface. The monomer that will be anchored in the metal was successfully prepared, remaining synthetize the monomer with an appropriate structure to perform the recognition of molecules and for catalysis
134

Superfícies magnéticas de campos helicoidais toroidais em tokamaks. / Magnetic surfaces of toroidal helical fields in tokamaks.

Monteiro, Luiz Henrique Alves 23 October 1990 (has links)
Propõe-se analisar teoricamente a instabilidade disruptora que ocorre em plasmas confinados em Tokamaks, investigando-se a influencia de campos helicoidais ressonantes em seu equilíbrio. Para isso, considerou-se a superposição do campo magnético do plasma em equilíbrio MHD estático com o campo associado às ressonâncias, levando-se em conta a geometria toroidal do Tokamak. Devido a falta de simetria, as linhas do campo magnético total resultante desta superposição devem formar superfícies magnéticas apenas em algumas regiões do plasma. Usando o método da media, foram obtidas (analiticamente) funções de superfícies aproximadas que contem, em torno das regiões de ressonância do plasma, as linhas deste campo magnético total. Verificou-se que estas superfícies aproximadas têm estruturas de ilhas magnéticas. / It is proposed to analyse theoretically the disruptive instability that occurs in confined plasmas in Tokamaks, through investigation of the influence of resonant helical fields on their equilibrium. With this aim, a superposition of the magnetic field of the plasma in static MHD equilibrium with the field associated with the resonances is considered, taking into account the toroidal geometry of the tokamak. Due to the lack of symmetry, the lines of the total magnetic field resulting from this superposition must form magnetic surfaces only around some regions of the plasma. Using the averaging method, functions of approximate magnetic surfaces are obtained (analitically) around the regions of resonances of the plasma (they contain the lines of this total magnetic field). It was verified that these approximate surfaces have structures of magnetic islands.
135

"Avaliação inter-observador da aplicação da sinuscopia virtual, comparada com as imagens obtidas por meio da tomografia computadorizada helicoidal, nos comprometimentos sinusais" / Interobserver evaluation of the virtual sinuscopy application compared with the images obtained by means of helical computerized tomography in sinusal compromise.

Freitas, Aurea do Carmo Pêpe Agulha de 18 April 2005 (has links)
Objetivo: Comparar as imagens obtidas por meio da sinuscopia virtual com aquelas adquiridas por meio da tomografia computadorizada helicoidal, quando da interpretação dos comprometimentos sinusais, considerando as opiniões dos médicos otorrinolaringologistas e radiologistas odontológicos, com a finalidade de validação do método da sinuscopia virtual. Métodos: Foram utilizadas informações obtidas por meio da observação de imagens de 20 casos pertencentes ao arquivo docente, da Unidade de Imagens Dento-Maxilo-Facial da Clínica Felix Boada, em Caracas-Venezuela. Os referidos casos apresentaram imagens adquiridas por meio da tomografia computadorizada helicoidal e imagens obtidas por meio da sinuscopia virtual. As imagens foram analisadas por 2 grupos de observadores, 10 médicos otorrinolaringologistas e 10 radiologistas odontológicos, que responderam a um questionário previamente elaborado. Resultados: Os resultados foram avaliados pelos testes estatísticos de média aritmética, mediana, desvio padrão, análise de médias, percentuais globais, teste não–paramétrico de Kruskal-Wallis e teste não-paramétrico de Wilcoxon. Conclusões: Para os médicos otorrinolaringologistas e radiologistas odontológicos faz-se importante, a associação das imagens obtidas por meio da sinuscopia virtual com as imagens axiais obtidas por meio da tomografia computadorizada helicoidal na interpretação de um comprometimento sinusal. Os radiologistas odontológicos acharam que as imagens axiais obtidas por meio da tomografia computadorizada helicoidal já eram esclarecedoras, na avaliação dos casos, embora também recomendassem a sinuscopia virtual. Nos casos considerados fáceis, a aplicação da sinuscopia virtual foi evidente, porém nos casos difíceis não contribuiu. A sinuscopia virtual isoladamente não oferece condições para a conclusão do diagnóstico de uma afecção sinusal. / Purpose: To compare the images obtained by means of virtual sinuscopy with those formed by means of helical computerized tomography during the interpretation of sinusal compromise taking into consideration the opinions of otorhinolaryngologists and odontological radiologists aiming to validate the method of virtual sinuscopy. Methods: Information obtained through the observation of images of 20 cases belonging to the professorial file, of the Dental – Maxillo - Facial Unit of Images of Félix Boada Clinic in Caracas–Venezuela were used. The cases mentioned above showed images formed by means of the helical computerized tomography and images formed by means of the virtual sinuscopy. The images were analysed by 2 groups of observers, 10 otorhinolaryngologists and 10 odontological radiologists who answered a questionnaire previously prepared. Results: The results were appraised through statistical tests of arithmetic average, median, standard deviation, average analysis, global percentile, Kruskal-Wallis non-parametric test and Wilcoxon non-parametric test. Conclusions: To the otorhinolaryngologists and odontological radiologists it is important, the association of the images obtained by means of the virtual sinuscopy with the axial images formed by means of helical computerized tomography in the interpretation of a sinusal compromise. The odontological radiologists thought the axial images formed by means of the helical computerized tomography were already elucidatory, for the evaluation of the cases although they also recommended the virtual sinuscopy. In the cases regarded as easy ones, the application of the virtual sinuscopy was evident, but in the difficult cases it didn’t contribute. The virtual sinuscopy used singly doesn’t offer conditions for a diagnostic conclusion of the sinusal affection.
136

Síntese e aplicações de polímeros helicoidais multifuncionalizados / Synthesis and applications of functionalized helical polymers

Sakae, George Hideki 29 November 2016 (has links)
Nesta tese foram feitos estudos cujo objetivo principal foi centrado na síntese, caracterização e estudos da morfologia e das aplicações de polímeros helicoidais fenilacetilênicos contendo grupos laterais opticamente ativos. O trabalho foi dividido em 3 capítulos. O primeiro consistiu do estudo de inserção da fração acetilênica em núcleos aril- e piridil-oxazolínicos. Algumas limitações experimentais foram observadas em função da funcionalização das porções monoméricas sob as condições de polimerização. O segundo estudo consistiu do controle de crescimento das cadeias poliméricas, por ação de nanopartículas tipo core-shell (Au@Te-NP\'s). Foi observado que sob tais condições obtém-se cadeias poliméricas substancialmente menores do que na ausência dessas partículas. O terceiro capítulo consistiu no uso de polímeros helicoidais derivados de prolina para catálise assimétrica de reações do tipo aldol. Os resultados se mostraram promissores. Esses estudos não foram concluídos mas foi possível obter produtos com altos excessos enantio- e diastereoisomericos. / This thesis aimed the synthesis, characterization, morphology studies and applications of phenylacetilenic helical polymers containing optically active pendant groups. The results are presented in three chapters. The first was centered on the functionalization of aril- and pyridil-oxazolines with the acetylenic portion. Some experimental limitations were faced because of the functionalization of the monomers under polymerization conditions. The second chapter was dedicated to the utilization of core-shell nanoparticles (Au@Te-NP\'s) on the control of polymer chain growth. The presence of these NPs ensures the production of substantially smaller polymeric chains. The third chapter was dedicated to the employment of the optically active helical polymers as catalysts for aldol type reactions. These studies couldn\'t be concluded but where very promissory leading to products with high enantio- and diastereomeric excess.
137

Efeitos da geometria toroidal na atuação de campos helicoidais ressonantes em Tokamaks / Toroidal geometry effects on the performance of resonant helical fields in Tokamaks

Silva, Elton Cesar da 01 March 2001 (has links)
Neste trabalho, consideramos os efeitos de um campo magnético ressonante externo sobre o plasma confinado em um tokamak. Este campo magnético pode ser produzido quer por condutores helicoidais ou por um limitador magnético caótico. O principal propósito desse campo magnético ressonante é criar uma região de linhas de força caóticas na borda da coluna de plasma que pode melhorar o confinamento do plasma. O campo magnético de equilíbrio foi obtido resolvendo-se a equação de GRAD-SHAFRANOV em um sistema de coordenadas intrinsecamente toroidal (as coordenadas polares toroidais). Obtivemos o campo magnético, gerado pelos condutores helicoidais, através da solução explícita da equação de LAPLACE no mesmo sistema de coordenadas. A partir desse campo magnético, tomando o termo de mais baixa ordem, obtivemos analiticamente um mapa estroboscópico simplético para um conjunto de anéis limitadores magnéticos caóticos. Calculamos esse mapa estroboscópico simplético usando uma formulação hamiltoniana e adotando a. ação dos limitadores magnéticos caóticos como uma sequência de pulsos do tipo função delta. Com esse mapa estroboscópico simplético, caracterizamos algumas ilhas magnéticas ressonantes e a transição para um regime de caos global através da superposição das mesmas. Usamos esse mapa estroboscópico simplético para estudar o transporte das linhas de força na borda da coluna de plasma. A perda de linhas de força caóticas, que atingem a parede interna do tokamak, segue uma distribuição de POISSON. Calculamos, ainda, o número médio de voltas, ao redor da câmara de vácuo, necessárias para que uma linha de força caótica atinja a parede da câmara. / In this work, we have considered the effects of an external resonant magnetic field on the plasma confined in a tokamak. This resonant field can be produced by helical windings or by a chaotic magnetic limiter. The main purpose of this resonant magnetic field is to create a region of chaotic field lines at the edge of the plasma that can improve the confinement of the plasma. The equilibrium tokamak field was obtained by solving the GRAD-SHAFRANOV equation in an intrinsically toroidal coordinate system (the toroidal polar coordinates). We have obtained the magnetic field which has been generated by helical windings through an explicit solution of the LAPCACE equation in the same coordinate system. From this magnetic field, taken in its lowest order, we have analytically obtained a sympletic stroboscopic map for a set of chaotic magnetic limiters. We have calculated this sympletic stroboscopic map by using a Hamiltonian formulation and by supposing the action of the chaotic magnetic limiters as a sequence of delta-function pulses. With this sympletic stroboscopic map we have characterized some resonant magnetic islands and the onset of global chaos through their overlap. We have used this sympletic stroboscopic map in order to study the transport of the field lines at the edge of the plasma. The loss of chaotic field lines that reach the inner wall of the tokamak follows a POISSON distribution. We have also calculated the average number of toroidal turns for a chaotic field line to reach the inner wall of the tokamak.
138

Síntese e aplicações de polímeros helicoidais multifuncionalizados / Synthesis and applications of functionalized helical polymers

George Hideki Sakae 29 November 2016 (has links)
Nesta tese foram feitos estudos cujo objetivo principal foi centrado na síntese, caracterização e estudos da morfologia e das aplicações de polímeros helicoidais fenilacetilênicos contendo grupos laterais opticamente ativos. O trabalho foi dividido em 3 capítulos. O primeiro consistiu do estudo de inserção da fração acetilênica em núcleos aril- e piridil-oxazolínicos. Algumas limitações experimentais foram observadas em função da funcionalização das porções monoméricas sob as condições de polimerização. O segundo estudo consistiu do controle de crescimento das cadeias poliméricas, por ação de nanopartículas tipo core-shell (Au@Te-NP\'s). Foi observado que sob tais condições obtém-se cadeias poliméricas substancialmente menores do que na ausência dessas partículas. O terceiro capítulo consistiu no uso de polímeros helicoidais derivados de prolina para catálise assimétrica de reações do tipo aldol. Os resultados se mostraram promissores. Esses estudos não foram concluídos mas foi possível obter produtos com altos excessos enantio- e diastereoisomericos. / This thesis aimed the synthesis, characterization, morphology studies and applications of phenylacetilenic helical polymers containing optically active pendant groups. The results are presented in three chapters. The first was centered on the functionalization of aril- and pyridil-oxazolines with the acetylenic portion. Some experimental limitations were faced because of the functionalization of the monomers under polymerization conditions. The second chapter was dedicated to the utilization of core-shell nanoparticles (Au@Te-NP\'s) on the control of polymer chain growth. The presence of these NPs ensures the production of substantially smaller polymeric chains. The third chapter was dedicated to the employment of the optically active helical polymers as catalysts for aldol type reactions. These studies couldn\'t be concluded but where very promissory leading to products with high enantio- and diastereomeric excess.
139

Numerical study of helical vortices and their instabilities / Étude numérique des instabilités de tourbillons hélicoïdaux

Selçuk, Savas Can 09 May 2016 (has links)
Le travail présenté dans ce mémoire est une contribution à l'étude numérique des systèmes tourbillonnaires hélicoïdaux qui sont émis dans le sillage des rotors (éoliennes, hélicoptères,...) et de leurs instabilités. Ici, ces écoulements sont localement modélisés par un ensemble de tourbillons à symétrie hélicoïdale. À l'aide d'un code de simulation numérique directe dédié, des solutions de base quasi-stationnaires sont obtenues pour différents systèmes tourbillonnaires. Une caractérisation précise et détaillée de ces solutions est ensuite effectuée : vitesse de rotation, taille et ellipticité du cœur, structure des champs de vitesse et de vorticité... À l'aide d'un algorithme d'Arnoldi couplé à une version linéarisée du code, on détermine les modes dominants d'instabilité ayant la même symétrie que l'écoulement de base, en fonction des paramètres du système: nombre de vortex, pas hélicoïdal, taille de cœur, nombre de Reynolds et présence d'un vortex de moyeu. En dessous d'un certain pas hélicoïdal critique, l'instabilité est dominée par un mode de déplacement global analogue au mode d’appariement d'une allé infinie de points vortex ou d'anneaux tourbillonnaires. En régime non linéaire, ce mode est à l'origine d'une dynamique complexe du système: dépassements, saute-mouton et fusion. On utilise un autre code linéarisé pour déterminer les modes instables qui brisent la symétrie hélicoïdale de l'état de base, caractérisés par une longueur suivant l'axe. À faible nombre d'onde, ces modes induisent localement des rapprochements entre portions de spires voisines. À grand nombre d'onde, on observe un autre type de mode qui déforme les cœurs tourbillonnaires via l'instabilité elliptique. / The work presented in this manuscript is a contribution to the numerical study of helical vortex systems and their instabilities, as encountered in the near wake of rotors (wind turbines, helicopters,~...). In this work, such flows are locally modelled within the framework of helical symmetry. Using a dedicated DNS code, helical quasi-stationary basic state solutions are obtained for several configurations, and accurate tools for their characterisation are developed: angular velocity, core size and ellipticity, structure of the velocity and vorticity fields... An Arnoldi algorithm is then coupled to a linearised version of the code. The dominant instability modes with the same symmetry as the base flow are extracted as a function of the system parameters: number of vortices, helical pitch, core size, Reynolds number, presence of a central hub vortex. Under a critical helical pitch, the instability is dominated by a global displacement mode analogous to the pairing mode of an infinite array of point vortices or vortex rings. In the nonlinear regime, this mode gives rise to complex dynamics: overtaking events, leapfrogging and merging. Another linearised code is then used to extract modes characterised by a wavelength along the helix, which break the helical symmetry of the base flow. At low wavenumbers, these modes induce local displacements of the vortices and bring together portions of neighbouring coils. At large wavenumbers, another type of mode is found, which deforms the vortex cores through the elliptical instability mechanism.
140

Rôle des prolines des hélices 2 et 5 dans le mécanisme d’activation des récepteurs couplés aux protéines G : Exemples du récepteur de la thyrotropine et du récepteur 2 de la vasopressine / Role of proline residues in helices and 5 for the activation mecanism of the G-protein coupled receptors : examples of the thyrotropin receptor and the vasopressin 2 receptor.

Chantreau, Vanessa 15 December 2014 (has links)
Objectifs : Les Récepteurs Couplés aux Protéines G (RCPG) constituent une grande famille ubiquitaire. Leur structure est caractérisée par sept hélices transmembranaires. Les déformations de ces hélices jouent un rôle majeur dans l’activation de ces récepteurs. La plupart de ces déformations sont liées à la présence de prolines conservées. Cependant, les prolines de l’hélice 2 et 5 des RCPG ne sont pas systématiquement présentes. De plus, la position de la proline dans l’hélice 2 est variable (2.58, 2.59 ou 2.60). Nous nous intéressons aux rôles des prolines des hélices 2 et 5 dans l’activation de deux RCPG : le récepteur de la thyrotropine (TSHR) et le récepteur 2 de la vasopressine (V2R). Méthodes : pour le TSHR et le V2R, nous concevons et caractérisons des mutants pour chaque position conservée de la proline dans l’hélice 2 et/ou 5, ainsi que des mutants sans proline. Résultats : Les mutants du TSHR n’ont pas le même comportement en termes d’expression, de glycosylation ou d’activité. La position la mieux tolérée, 2.59, nous permet de rapprocher le TSHR des récepteurs avec une proline en position 2.59 qui possèdent un renflement dans l’hélice 2. Pour l’hélice 5, les données expérimentales couplées à l’analyse des séquences et la modélisation moléculaire suggèrent une structure non renflée. Pour le V2R, le changement de position de la proline de l’hélice 2 est plus délétère que l’absence de proline dans cette hélice. La proline de l’hélice 5 est indispensable pour l’activité de ce récepteur. Conclusion : Les données obtenues sur le TSHR permettent de proposer un modèle avec une hélice 2 renflée et une hélice 5 non renflée et d’améliorer la modélisation de la cavité interne de ce récepteur, ce qui est essentiel pour le drug design. L’étude du V2R permet de proposer un modèle évolutif de ce récepteur et met en évidence sa spécificité par rapport à des récepteurs proches. / Objectives : Class A G-Protein-coupled receptors (GPCRs) constitute a large family of transmembrane receptors. Helical distortions play a major role in the overall fold and in the activation mechanism of these receptors. Most distortions are related to the presence of conserved proline residues. However, in helices TM2 and TM5, the presence of proline is not mandatory and the correlated mutation of these proline residues is observed in several GPCR sub-families. In addition, the position of the TM2 proline is variable (2.58 to 2.60). We are interested in the role of the TM2 and TM5 proline residues in the folding and activation mechanism of two GPCRs : the thyrotropin receptor (TSHR) and the vasopressin receptor type 2 (V2R). Methods : For both receptors, we engineered and characterized mutants with proline residues at different positions in TM2 and/or at position 5.50 in TM5, and without proline. Results : The expression, the glycolysation or the activity of TSHR mutants are differentially altered by changes in the proline pattern. The “best” mutant, TSHR P2.59, is consistent with a bulged structure for TM2. Experimental data in addition to sequences analysis and modeling suggest an unbulged structure for TM5. For V2R, the absence of proline in TM2 is better tolerated than ashift in the position. The TM5 proline is mandatory for the receptor activation. Conclusion : We suggest a model for TSHR with a bulged TM2 and an unbulged TM5. This should improve the modeling of the transmembrane cavity, which is fundamental for drug design. Our results on V2R suggest an evolutionary model for this receptor and enlighten its specificity compared to nearby receptors.

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