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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.
91

Design and Synthesis of Aspartic and Serine Protease Inhibitors : Targeting the BACE-1 and the HCV NS3 Protease

Wångsell, Fredrik January 2009 (has links)
This thesis describes work done to design and synthesize protease inhibitors, with the intention of developing therapeutic agents for Alzheimer’s disease (AD) and the chronic liver condition caused by infection of the hepatitis C virus (HCV). AD is the most common form of dementia, and HCV infection is the primary reason for liver transplantation in industrialized countries. Today, these two illnesses affect 24 and 170 million people, respectively. It has been shown that the human aspartic protease BACE-1 plays an important role in the development of AD, and thus inhibition of BACE-1 may offer a way to improve the quality of life of individuals afflicted with the disease. Furthermore, it is known that the serine protease NS3 is a vital component in the replication of HCV. Several novel potent BACE-1 inhibitors encompassing different transition state mimics were prepared. First, a hydroxyethylene moiety encompassing a secondary hydroxyl group was evaluated as a transition state analogue, producing inhibitors in the low nanomolar range. Various tertiary hydroxyl isosteres were also investigated as the central core, with the aim of shielding the pivotal hydroxyl group. These transition state isosteres consisted of tertiary hydroxyl analogues of previously used secondary hydroxyl containing norstatine, statine, and hydroxyethylamine isosteres. Several tertiary hydroxyl-containing inhibitors were found to be active in the low micromolar range. In addition, two inhibitors were co-crystallized with the BACE-1 enzyme to provide X-ray crystal structures, which furnished valuable binding information for further design of improved BACE-1 inhibitors. The goal in the HCV NS3 protease inhibitor project was to design, synthesize and evaluate a novel hydroxycyclopentene bioisostere to the previously used acyl-hydroxyproline moiety. The investigation revealed that it was possible to synthesize inhibitors containing this new bioisostere that were potent in the low nanomolar range. Further optimization by rigidification of the most active inhibitor resulted in equipotent macrocyclic compounds.
92

Extraction of High-Value Minor Proteins from Milk

Billakanti, Jaganmohan January 2009 (has links)
Various methods for extraction and analysis of high value minor proteins (lactoferrin, lactoperoxidase and immunoglobulins) directly from raw milk were explored. Extraction, purification and analysis of high-value minor proteins directly from milk without pre-treatment are major challenges for dairy industry, largely due to the complexity of milk and the presence of colloidal solids (casein micelles and milk fat globules). To overcome some of these challenges, this work focused on three main objectives: 1) characterization of cryogel monolith chromatography for purification of lactoferrin (LF) and lactoperoxidase (LP) directly from raw milk in single step, 2) identification and characterization of Protein A Mimetic affinity ligands for purification of immunoglobulins (Igs) from milk and 3) development and validation of a surface plasmon resonance method for simultaneous quantification of five whey proteins in multiple samples. Results portrayed the possibility of 40–50 column volumes of various milk samples (whole milk, skim milk and acid whey) to pass through a 5 mL cryogel monolith chromatography column at 525 cm hr⁻¹ without exceeding its pressure limits if the processing temperature is maintained around 35–37°C. Ideally, this should be the milk secretion temperature. The dynamic binding capacity obtained for the cryogel matrix (2.1 mg mL⁻¹) was similar to that of the binding capacity (2.01 mg mL⁻¹) at equilibrium with 0.1 mg mL⁻¹ of lactoferrin in the feed samples. Lactoferrin and lactoperoxidase was selectively bound to the cryogel column with trivial leakage in flowthrough fractions. Lactoferrin was recovered from elution fractions with a yield of 85% and a purity of 90%. These results, together with the ease of manufacture, low cost and versatile surface chemistry of cryogels suggest that they may be a good alternative to packed-bed chromatography for direct capture of proteins from milk, provided that the binding capacity can be increased. A Protein A Mimetic (PAM) hexapeptide (HWRGWV) peptide ligand that binds to the Fc portion of antibody molecules was explored for affinity purification of immunoglobulins from milk. The peptide has the ability to purify IgG from various milk and whey samples with a purity of greater than 85% in single step. More than 90% bound IgG was recovered with 0.2 M acetate buffer at pH 4.0 and total column regeneration was successfully achieved by 2.0 M guanidine-HCl. At 9.0 mg mL⁻¹ of IgG feed concentration, an equilibrium binding capacity of 21.7 mg mL⁻¹ and dynamic binding capacity of approximately 12.0 mg mL⁻¹ of resin was obtained. Recoveries and yields of IgG were significantly influenced by the feed IgG concentration. PAM hexamer ligand also contributed a significant amount of cross-reactivity with casein, glycomacropeptides and β-lactoglobulin proteins, however majority of these proteins were recovered in the regeneration step, except β-lactoglobulin, which co-eluted with IgG. Higher IgG concentration in feed vastly reduced the amount of cross-reactivity whilst increasing the recoveries and purities in the final product. PAM affinity ligands also showed interactions towards other classes of bovine immunoglobulins. These findings established the possibility of using PAM hexamer peptide as an alternative to conventional Protein A/G affinity chromatography for the isolation of Igs from milk in single step process. A surface plasmon resonance (SPR) method was developed for simultaneous, quantitative determination of commercially important whey proteins in raw and processed milk samples, whey fractions and various milk-derived products, with six samples per assay. Immobilized antibody stability and reproducibility of analyses were studied over time for 25 independent runs (n=300), giving a relative standard deviation (RSD) of <4%. Immobilized antibodies showed negligible non-specific interactions (<2–4 SPR response units (RU)) and no cross-reactivity towards other milk components (<1 RU). Regeneration of immobilised antibodies with glycine at pH 1.75 was determined to be optimal for maintaining the SPR response between samples. This method compared and validated well with reversed phase high performance liquid chromatography (RP-HPLC) and standard enzyme-linked immunosorbent assays (ELISA).
93

Σχεδιασμός και υλοποίηση συστήματος αυτοματισμού συγκροτήματος φαρίνας ΠΚ4 και ΠΚ5 με χρήση PLC, ανάπτυξη μιμητικών διαγραμμάτων (SCADA) και αντικατάσταση ηλεκτρολογικών διανομών στο εργοστάσιο «Όλυμπος» της ΑΓΕΤ Ηρακλής

Ανέστης, Κυριάκος 16 June 2011 (has links)
Η παρακάτω διπλωματική εργασία περιλαμβάνει την περιγραφή των εργασιών που πραγματοποιήθηκαν κατά τον εκσυγχρονισμό του συστήματος αυτοματισμού των σιλό φαρίνας Δ και Ε. Αρχικά περιγράφεται περιληπτικά η διαδικασία παραγωγής του τσιμέντου και ο ρόλος των σιλό φαρίνας Δ και Ε στη γραμμή παραγωγής. Στη συνέχεια αναλύεται η μετάβαση από τον κλασσικό αυτοματισμό στη χρήση Προγραμματιζόμενου Λογικού Ελεγκτή (PLC) και αναφέρονται οι σημαντικότερες αλλαγές που συνέβησαν. Το επόμενο κομμάτι της εργασίας αναφέρεται στο διάγραμμα ροής του συγκροτήματος φαρίνας ΠΚ4 και ΠΚ5 όπου παρατίθεται σχετικό σχεδιάγραμμα με τη ροή του υλικού ενώ επιπροσθέτως περιγράφεται η λειτουργία όλων των μηχανών που περιλαμβάνονται σ’ αυτό. Έπειτα γίνεται μετάβαση στη λογική αυτοματισμού που αναπτύχθηκε από τους μηχανικούς αυτοματισμού του εργοστασίου όπου περιγράφονται όλες οι είσοδοι και οι έξοδοι του PLC, το πρόγραμμα που χρησιμοποιήθηκε και ο κώδικας προγράμματος που δημιουργήθηκε. Αμέσως μετά γίνεται ξεχωριστή αναφορά στο μιμητικό διάγραμμα (SCADA) με παράθεση των εικόνων που το αποτελούν και επεξήγηση όλων των ενδείξεων και επιλογών που περιλαμβάνει. Στη συνέχεια αναφέρονται τα δίκτυα που χρησιμοποιήθηκαν για τον έλεγχο της μονάδας των σιλό Δ και Ε, δηλαδή το βιομηχανικό δίκτυο Profibus και το δίκτυο Ethernet, όπου περιγράφεται ο τρόπος επικοινωνίας των χειριστών της μονάδας με τις μηχανές της διεργασίας. Το τελευταίο τμήμα της εργασίας περιλαμβάνει την βήμα προς βήμα περιγραφή των εργασιών ως την ολοκλήρωση του έργου, τη διαδικασία του τελικού ελέγχου του έργου καθώς και μια σύντομη αναφορά στη συμμετοχή του φοιτητή σε τμήμα των παραπάνω εργασιών. Η διπλωματική εργασία κλείνει με την παράθεση των πηγών καθώς και ορισμένων συμπληρωματικών παραρτημάτων. / The following thesis includes a description of the work carried out during the modernization of the automation system of raw meal silo D and E. Firstly it is described briefly the production process of cement and the role of raw meal silo D and E on the production line. Afterwards the transition from classical automation to the use of a Programmable Logic Controller (PLC) and some of the most significant changes occurred are analyzed. In the next chapter it is reported the complex flow of raw meal PK4 and PK5 citing a diagram with the flow of material and furthermore the operation of all machinery therein is described. Following there is a shift in the automation logic developed by automation engineers of the factory describing all inputs and outputs of the PLC, the program used and the program code created. A separate reference to mimetic diagram (SCADA) follows including the images that constitute it and an explanation of all the indications and options included. The next chapter includes the networks used for the control unit of the silo D and E, which are the Profibus industrial network and the network Ethernet, where it is described the way in which the operator of the plant contacts with the machinery of the process. The last part of the thesis includes step-by-step the description of the works as the project is completed, the process of final verification of the project and a brief reference to the student’s involvement. The thesis concludes with a statement of sources and some additional annexes.
94

Le chant de la violence collective : l'imaginaire persécuteur dans les versions françaises de la "Chanson de Roland" / The song of collective violence : a study of prosecutor imaginary in the French versions of the Song of Roland

Dijoux, Mathieu 04 June 2015 (has links)
La thèse entend proposer un commentaire de la Chanson de Roland, fondé sur l'analyse minutieuse de toutes les variantes qui nous soient parvenues. Cette prise en considération de l'ensemble des versions françaises, rompant avec le dogme de la précellence du manuscrit d'Oxford, s'explique logiquement par la nature mouvante des œuvres médiévales, mais s'enracine aussi dans la conviction d'une texture mythique du poème de Roncevaux. Aussi le recours à la mythologie comparée constitue-t-il une ligne de force majeure du présent travail : s'inscrivant dans la tradition des études indo-européennes telles que Georges Dumézil a contribué à les fonder, la thèse propose une comparaison morphologique entre les mythes de Baldr et de Roland. Cet essai de mythologie comparée forme un premier temps dans l'analyse de la texture mythique du poème et peut être considéré comme autonome. Il s'articule cependant avec le travail de comparaison typologique qui lui succède. La thèse se propose en effet d'étudier la Chanson de Roland à la lumière de l'hypothèse victimaire élaborée par René Girard, qui permet de penser sous un jour nouveau l'esthétique et l'idéologie de la chanson de geste. De fait, la poétique de la répétition et l'art de la symétrie sont justiciables de la théorie du désir mimétique, tout comme la crise épique entretient des analogies étroites avec le modèle de la crise sacrificielle. C'est autour de la question anthropologique de la violence et de l'ambiguïté de la figure du guerrier mythique que ce travail réconcilie deux méthodes réputées incompatibles et pourtant complémentaires dans l'analyse qu'elles proposent de l'ambivalence des héros épiques. / This doctoral thesis intends to propose a commentary of the Chanson de Roland, based on a meticulous analysis of all the variants which have reached posterity. By paying close attention to the whole of French versions and by refusing to comment the sole manuscript of Oxford, as most of scholars do, we comply with the unsettled nature of medieval poetry and furthermore support the idea that the Chanson de Roland should be considered as a myth. The comparative mythology thus constitutes a main thrust of this work : in the tradition on Indo-european studies as founded by Georges Dumézil, we compare the myth of Roland to the myth of Balder, on a morphological level. The essay of comparative mythology is the first part of our commentary and could be regarded as self-reliant. However, it forms a single entity with the essay of typological comparison which follows. The thesis actually intends to interpret the poem in the light of the theory developed by René Girard, which allows to analyze the aesthetics and the ideology of the chanson de geste in a new light. The poetic of repetition and the art of symmetry are closely linked to the hypothesis of mimetic desire, just like the epic crisis is closely linked to the model of the sacrificial crisis. By studying the anthropological question of violence and the ambiguous figure of mythical warrior, this work combines two approaches, deemed to be irreconcilable and nevertheless complementary, in the sense that they interpret in the same way the ambivalence of epic heroes.
95

SILAS MALAFAIA: SEUS DESEJOS E MODELOS Um estudo a partir da teoria do desejo mimético de René Girard / Silas Malafaia: your desires and models. a study from the theory of mimetic desire Rene Girard

SOUZA, GIDEANE MORAES DE 20 September 2016 (has links)
Submitted by Noeme Timbo (noeme.timbo@metodista.br) on 2017-01-26T12:02:47Z No. of bitstreams: 1 GideanaSousa.pdf: 2682729 bytes, checksum: 5ec57ecb335f020e008c123896e1f756 (MD5) / Made available in DSpace on 2017-01-26T12:02:47Z (GMT). No. of bitstreams: 1 GideanaSousa.pdf: 2682729 bytes, checksum: 5ec57ecb335f020e008c123896e1f756 (MD5) Previous issue date: 2016-09-20 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / This dissertation presents the results of research on Silas Malafaia - a well-known lecturer between evangelicals and among non- evangelicals in Brazil that uses the TV feature for about 33 years , where it holds programs with different formats over the years ; and an incisive speech relevant influence on many followers . His preaching condemns abortion , drug use and what sees as increasing the privileges of homosexuals , while he took the theology of prosperity. Using the theory of Mimetic Mechanism René Girard , and studying the context in which it was created and who was related from its beginnings , this research studies the evolution and positioning changes Silas Malafaia and the influence of his desire models. We will analyze in particular the transition to a more conservative theology Assembly of God to join the Positive Confession and Prosperity Theology, and the use of media not only toward Christians, but as a trade tool , which once fought . It started from the hypothesis that Silas Malafaia change his speech and preaching in that it takes as models of desire televangelists American pastors , as Morris Cerullo and Mike Murdock , who work in television media and are considered successful pastors. That the analysis , we differentiate two types of desire models - according to the mimetic desire theory of René Girard - in the life of Silas Malafaia : internal mediation models and external mediation. It is hoped that this work can contribute to the reflections on René Girard 's theory and for studies concerning the Assembleiano Pentecostalism and its various possibilities. / Esta dissertação de mestrado apresenta os resultados da pesquisa sobre Silas Malafaia – um conferencista conhecido entre evangélicos e entre não-evangélicos no Brasil que se utiliza do recurso televisivo há cerca de 33 anos, onde detém programas com formatos diversificados ao longo dos anos; e um discurso incisivo de relevante influência sobre muitos seguidores. Sua pregação condena o aborto, o uso de drogas e o que enxerga como aumento dos privilégios dos homossexuais, ao mesmo tempo em que assumiu a teologia da prosperidade. Usando da teoria do Mecanismo Mimético de René Girard, e estudando o contexto no qual foi criado e com quem se relacionou desde os seus primórdios, esta pesquisa estuda a evolução e mudanças de posicionamento de Silas Malafaia e a influência dos seus modelos de desejo. Analisaremos em particular a sua transição de uma teologia mais conservadora da Assembleia de Deus para adesão à Confissão Positiva e Teologia da Prosperidade, e a utilização da Mídia não apenas voltada para cristãos, mas como ferramenta de comercio, que antes combatia. Parte-se da hipótese de que Silas Malafaia muda seu discurso e pregação na medida em que assume como modelos de desejo pastores norte-americanos teleevangelistas, como Morris Cerullo e Mike Murdock, que atuam na mídia televisiva e são considerados pastores bem-sucedidos. Nessa na análise, diferenciamos dois tipos de modelos de desejo, -- de acordo com a teoria de desejo mimético de René Girard -- na vida de Silas Malafaia: modelos de mediação interna e os de mediação externa. Espera-se que este trabalho possa contribuir para as reflexões sobre a teoria de René Girard e também para estudos concernentes ao Pentecostalismo Assembleiano e suas diversas possibilidades.
96

Tramas, teias e jogos dramáticos em Edward Albee, Patrick Marber e Mike Nichols

Zanesco, Liane Mroginiski January 2010 (has links)
O presente trabalho explora a questão da interdisciplinaridade e da transposição de obras literárias para o cinema. Focalizando a adaptação de textos dramáticos ao cinema, o estudo propõe em um primeiro momento uma investigação teórica sobre gênero ficcional mimético; drama, a partir da perspectiva do jogo dramático como elemento construtor do metadrama implícito e explícito; transtextualidade e cinema. Num segundo momento, a investigação analisa dois textos dramáticos, Who’s afraid of Virginia Woolf? , de Edward Albee, e Closer , de Patrick Marber, e suas respectivas transposições para o cinema pelo diretor Mike Nichols, examinando os elementos e recursos que os autores utilizam para construir o jogo dramático. Posteriormente, realizase uma análise comparativa entre os textos dramáticos e entre suas adaptações cinematográficas, buscando pontos de contato e de afastamento entre as obras, priorizando elementos denotadores do jogo dramático, além de características transtextuais que possibilitam a manutenção ou a alteração de significados entre os textos dramáticos e seus respectivos filmes. / This paper explores interdisciplinary aspects related to the transposition of dramatic texts into films. First, a theoretical investigation is conducted on mimetic genre, transtextuality; on drama, from the point of view of the game as a dramatic element to build implicit and explicit metadrama, and film adaptation. Secondly, this dissertation analyzes two plays, Who's afraid of Virginia Woolf? , by Edward Albee, and Closer , by Patrick Marber, as well as their film adaptations by director Mike Nichols, and examines the elements and features that the authors use to create the dramatic games. Later, the plays and their film adaptations are contrasted in order to investigate elements of dramatic games, and transtextual characteristics that allow the maintenance or the alteration of meaning between the plays and their correspondent films.
97

ESPIRITUALIDADE E EDUCAÇÃO PARA A LIBERDADE: o opressor hospedado no oprimido de Paulo Freire e a teoria do desejo mimético de René Girard

Soares, Adriana 15 September 2008 (has links)
Made available in DSpace on 2016-08-03T12:20:47Z (GMT). No. of bitstreams: 1 Adriana Soares.pdf: 761404 bytes, checksum: 44e300758f15bb12eef253d08552ae45 (MD5) Previous issue date: 2008-09-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study discusses the relationship between spirituality and education for freedom from the anthropological perspective of human mimetic desire as key to the understanding of human relations, and spirituality as a fundamental dimension in the engagement in the battle for transformation of society. Through literature search, it is the analysis of the problem identified by Paulo Freire, that the oppressive "hosted" the oppressed represents an obstacle to the liberation, from the perspective of the theory of mimetic desire of René Girard. Works with the hypothesis that this essential element in anthropological thinking of Paulo Freire, forgotten as his pedagogical proposal assumed a character purely on conscience, refers to the dimension of spirituality. Because the distance between utopia of the liberation and the reality, establishes itself the scene of a crisis that falls not only on formal educators, but also on many of those who, at some point in their lives, whether in the battle for the engagement in social transformation. Since the method is well known, and it is acquire consciousness, the fact that the dreamed transformation has not occurred leads the conclusion that something failed in the process.(AU) / Este estudo discute a relação entre espiritualidade e educação para a liberdade, a partir da perspectiva antropológica da natureza mimeticamente desejante do ser humano como elemento chave para a compreensão das relações humanas, e da espiritualidade como dimensão fundamental para o engajamento na luta pela transformação da sociedade. Por meio de pesquisa bibliográfica, procede-se à análise do problema identificado por Paulo Freire, de que o opressor hospedado no oprimido representa um obstáculo para a libertação, sob a ótica da teoria do desejo mimético de René Girard. Trabalha-se com a hipótese de que o elemento antropológico fundamental presente no pensamento de Paulo Freire, esquecido à medida que sua proposta pedagógica assumiu um caráter meramente conscientizador, referese à dimensão da espiritualidade. Diante do abismo que se coloca entre a utopia da libertação e a realidade instaura-se o cenário de crise que recai, não apenas sobre educadores formais, como também sobre muitos daqueles que, em algum momento de suas vidas, se engajaram na luta pela transformação social. Uma vez que o método é sabido, e é conscientizar, o fato de que a transformação sonhada não tenha ocorrido leva a conclusão de que alguma coisa falhou no processo.(AU)
98

Tramas, teias e jogos dramáticos em Edward Albee, Patrick Marber e Mike Nichols

Zanesco, Liane Mroginiski January 2010 (has links)
O presente trabalho explora a questão da interdisciplinaridade e da transposição de obras literárias para o cinema. Focalizando a adaptação de textos dramáticos ao cinema, o estudo propõe em um primeiro momento uma investigação teórica sobre gênero ficcional mimético; drama, a partir da perspectiva do jogo dramático como elemento construtor do metadrama implícito e explícito; transtextualidade e cinema. Num segundo momento, a investigação analisa dois textos dramáticos, Who’s afraid of Virginia Woolf? , de Edward Albee, e Closer , de Patrick Marber, e suas respectivas transposições para o cinema pelo diretor Mike Nichols, examinando os elementos e recursos que os autores utilizam para construir o jogo dramático. Posteriormente, realizase uma análise comparativa entre os textos dramáticos e entre suas adaptações cinematográficas, buscando pontos de contato e de afastamento entre as obras, priorizando elementos denotadores do jogo dramático, além de características transtextuais que possibilitam a manutenção ou a alteração de significados entre os textos dramáticos e seus respectivos filmes. / This paper explores interdisciplinary aspects related to the transposition of dramatic texts into films. First, a theoretical investigation is conducted on mimetic genre, transtextuality; on drama, from the point of view of the game as a dramatic element to build implicit and explicit metadrama, and film adaptation. Secondly, this dissertation analyzes two plays, Who's afraid of Virginia Woolf? , by Edward Albee, and Closer , by Patrick Marber, as well as their film adaptations by director Mike Nichols, and examines the elements and features that the authors use to create the dramatic games. Later, the plays and their film adaptations are contrasted in order to investigate elements of dramatic games, and transtextual characteristics that allow the maintenance or the alteration of meaning between the plays and their correspondent films.
99

Tramas, teias e jogos dramáticos em Edward Albee, Patrick Marber e Mike Nichols

Zanesco, Liane Mroginiski January 2010 (has links)
O presente trabalho explora a questão da interdisciplinaridade e da transposição de obras literárias para o cinema. Focalizando a adaptação de textos dramáticos ao cinema, o estudo propõe em um primeiro momento uma investigação teórica sobre gênero ficcional mimético; drama, a partir da perspectiva do jogo dramático como elemento construtor do metadrama implícito e explícito; transtextualidade e cinema. Num segundo momento, a investigação analisa dois textos dramáticos, Who’s afraid of Virginia Woolf? , de Edward Albee, e Closer , de Patrick Marber, e suas respectivas transposições para o cinema pelo diretor Mike Nichols, examinando os elementos e recursos que os autores utilizam para construir o jogo dramático. Posteriormente, realizase uma análise comparativa entre os textos dramáticos e entre suas adaptações cinematográficas, buscando pontos de contato e de afastamento entre as obras, priorizando elementos denotadores do jogo dramático, além de características transtextuais que possibilitam a manutenção ou a alteração de significados entre os textos dramáticos e seus respectivos filmes. / This paper explores interdisciplinary aspects related to the transposition of dramatic texts into films. First, a theoretical investigation is conducted on mimetic genre, transtextuality; on drama, from the point of view of the game as a dramatic element to build implicit and explicit metadrama, and film adaptation. Secondly, this dissertation analyzes two plays, Who's afraid of Virginia Woolf? , by Edward Albee, and Closer , by Patrick Marber, as well as their film adaptations by director Mike Nichols, and examines the elements and features that the authors use to create the dramatic games. Later, the plays and their film adaptations are contrasted in order to investigate elements of dramatic games, and transtextual characteristics that allow the maintenance or the alteration of meaning between the plays and their correspondent films.
100

Estudo teórico de interações não covalentes entre complexos trinucleares de platina (II) e DNA

Paixão, Nathália Magalhães 20 February 2017 (has links)
Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-05-15T14:18:18Z No. of bitstreams: 1 nathaliamagalhaespaixao.pdf: 3549646 bytes, checksum: dfd913fd20520fb3cbfe42b45a3b6f5f (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-17T15:59:23Z (GMT) No. of bitstreams: 1 nathaliamagalhaespaixao.pdf: 3549646 bytes, checksum: dfd913fd20520fb3cbfe42b45a3b6f5f (MD5) / Made available in DSpace on 2017-05-17T15:59:23Z (GMT). No. of bitstreams: 1 nathaliamagalhaespaixao.pdf: 3549646 bytes, checksum: dfd913fd20520fb3cbfe42b45a3b6f5f (MD5) Previous issue date: 2017-02-20 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Câncer é um processo de crescimento e disseminação incontrolado de células e tem sido considerado como uma questão de saúde pública. Os compostos polinucleares de Platina (II) têm se mostrado muito promissores contra células cancerosas devido a interações mais rápidas e efetivas em comparação com os compostos mononucleares, como por exemplo, o complexo BBR3464. A partir disso, diversos estudos vêm sendo realizados com intuito de descrever os modos de interação de tais compostos. Este trabalho tem como objetivo fornecer um estudo teórico sistemático do complexo trinuclear de platina (II), AH78, através do uso de diferentes níveis de cálculo. Os compostos trinucleares de platina (II) estudados nesse trabalho não são capazes de formar ligações covalentes com o DNA, interagindo através da formação de grampos de fosfato, que são preferencialmente interações de hidrogênio e eletrostáticas. Dessa forma, este trabalho teve como motivação avaliar a interação dos complexos trinucleares de platina (II) não covalentes com o DNA por meio da formação de grampos de fosfato, analisadas através de modelos miméticos demonstrando presença de tais interações a partir de uma análise mais rápida e eficaz. Foram obtidas estruturas contendo uma fração de DNA que contém 6 pares de bases nitrogenadas e o complexo AH78, utilizando o método ONIOM, que comprovam a existência dos grampos de fosfato entre o complexo e o DNA. / Cancer is a process of uncontrolled growth and spread of cells and has now been considered a public health issue. Polynuclear Platinum (II) Complexes (PPCs) have shown very promising against cancer cells because of faster and more effective interactions compared to mononuclear compounds, such as the BBR3464 complex. From this, several studies have been carried out to describe the modes of interaction of such compounds. This work provides an extensive and systematic theoretical study of the platinum (II) trinuclear complex, AH78, using different base set functions for C, N and H atoms, including diffusive and polarization functions and different ECPs for platinum. The platinum (II) trinuclear compounds studied in this work are not able to form covalent bonds with DNA, interacting by the formation of phosphate bonds, which are preferably hydrogen type and electrostatic interactions. Thus, this work had the motivation to evaluate the interaction of non-covalent platinum (II) trinuclear complexes with DNA by means of the formation of phosphate clamps, analyzed using mimetic models, demonstrating that the presence of such interactions from a faster analysis is efficient. Structures containing a DNA fraction were obtained with six purine base pairs and AH78 complex using the ONIOM method, which demonstrate the existence of the phosphate clamps between the complex and the DNA.

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