Дисертації з теми "Peptide toxin"
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Thompson, Christopher Hal. "Identification and characterization of a peptide toxin inhibitor of ClC-2 chloride channels." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/26604.
Повний текст джерелаCommittee Chair: McCarty, Nael; Committee Co-Chair: Harvey, Stephen; Committee Member: Hartzell, Criss; Committee Member: Kubanek, Julia; Committee Member: Lee, Robert. Part of the SMARTech Electronic Thesis and Dissertation Collection.
Ekberg, Jenny. "Novel peptide toxin and protein modulators of voltage-gated ion channels /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe20102.pdf.
Повний текст джерелаDroctove, Laura. "Premières toxines Kunitz antagonistes du récepteur de type 2 à la vasopressine : étude pharmacodynamique et relations structure-activité." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS009/document.
Повний текст джерелаMambaquaretin-1 (MQ-1), a green mamba toxin, is the very first Kunitz peptide to selectively hinder the vasopressin type 2 receptor (V2R) activation. This receptor controls the final concentration of urine in kidneys. Involved in a number of pathologies, its inhibition is currently considered as the best therapeutic strategy in the treatment of polycystic kidney disease, a hereditary genetic disease. Pharmacodynamic study of MQ-1 carried out on healthy rats confirmed its in vivo activity which consists in inducing a dose-dependent aquaretic effect. Maximum effect is reached 2 hours after an intraperitoneal injection and disappears in a biological half-life ranging from 1 to 4 hours according to the dose. The daily injection of small quantities pointed to a cumulative effect over the first three days, leading to a plateau, which suggests a residual activity exceeding 24 hours. The screening of the three other mamba venoms along with a comparative analysis of the closest peptide sequences reported in databases revealed the existence of a phylogenetic group of eleven V2R antagonist Kunitz toxins. An innovative approach combining binding assays on MQ-1 variants and the modelling of the MQ-1-V2R complex has led to a partial deciphering of the pharmacophore of the toxin. The two partners share a significant ionic complementarity involving a number of extracellular loops of the receptor, and a hydrophobic region of MQ-1 interacts within V2R in the vicinity of its supposed orthosteric site. Lastly, a collaboration initiated with a pharmaceutical company brought out the need for the closer scrutiny of some crucial points to succeed in a therapeutic development of MQ-1
Blagojevic, Mariana. "Epithelial cell death induced by Candidalysin, a cytolytic peptide toxin of Candida albicans." Thesis, King's College London (University of London), 2018. https://kclpure.kcl.ac.uk/portal/en/theses/epithelial-cell-death-induced-by-candidalysin-a-cytolytic-peptide-toxin-of-candida-albicans(7a2a83b3-dd43-472f-87b3-1d157687b440).html.
Повний текст джерелаJohnson, Stephen Roy. "A Biochemical And Pharmacological Characterization Of A Novel Neuroactive Peptide From The Neotropical Hunting Ant Dinoponera Australis." Available to subscribers only, 2009. http://proquest.umi.com/pqdweb?did=1879010761&sid=3&Fmt=2&clientId=1509&RQT=309&VName=PQD.
Повний текст джерела"Department of Pharmacology." Keywords: Peptides, Toxins, Venom, Neuroactive peptide, Neurotoxins. Includes bibliographical references (p. 200-210). Also available online.
Perez, Morales Tiara G. "Production of and Response to the Cannibalism Peptide SDP in Bacillus subtilis." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/4895.
Повний текст джерелаVoegele, Alexis. "Study of the translocation mechanism of the cyaa toxin from bordetella pertussis." Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/VOEGELE_Alexis_va.pdf.
Повний текст джерелаThe adenylate cyclase toxin (CyaA) is one of the major virulence factor produced by Bordetella pertussis, the causative agent of whopping cough. CyaA has the unique capacity to translocate its catalytic domain directly across the plasma membrane. Then, the catalytic domain binds to calmodulin (CaM) to produce high levels of cAMP, leading to cell intoxication. Although several models have been proposed, the molecular mechanism and the forces involved in the translocation of CyaA remain elusive. The calcium gradient, the membrane potential across the plasma membrane and post-translational acylation are required for an efficient CyaA translocation. During my PhD, I mainly investigated the translocation process. It has been previously shown that deletion of the translocation region abolishes the delivery of the catalytic domain into the cytosol of target cells. In this region, the peptide P454 (residues 454 to 484 of CyaA) was identified and exhibits membrane-active properties related to antimicrobial peptides, i.e membrane interaction, α-helical folding upon membrane insertion and membrane permeabilization. We have investigated the role of P454 on the translocation process. We observed that negatively charged and fluidic membrane favor P454 membrane insertion. The peptide contains two arginine residues that are critically involved in its membrane-active properties. We further identified that P454 exhibits the intrinsic propensity to translocate across lipid bilayers and forms a stable complex with CaM. We identified several residues from P454 involved in both membrane interaction and CaM binding. We showed in the context of the full-length CyaA toxin that these residues are essential for the efficient translocation of the catalytic domain into the cell and production of cAMP. We propose a translocation model in which the membrane-active P454 segment from the translocation region destabilizes the membrane, favoring its translocation. In the cytosol, the P454 segment is trapped by CaM and the formation of the complex may act as a driving force pulling the catalytic domain across the plasma membrane. We further showed that CaM binding to the main CaM-binding site in the catalytic domain induces local and long-range allosteric effects that stabilize the enzymatic site, allowing fast ATP catalysis to cAMP, leading to host subversion. The relevance of these results for the translocation and activation of CyaA are discussed
Wernecke, Julia [Verfasser]. "Biophysical characterisation of the fungal peptide toxin Ece1-III and its interaction with lipid membranes / Julia Wernecke." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2016. http://d-nb.info/1121535852/34.
Повний текст джерелаTisseyre, Céline. "La maurocalcine : substance naturelle d'intérêt thérapeutique." Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENV047/document.
Повний текст джерелаMaurocalcine (MCa) is a 33-mer toxin originally isolated from the venom of the scorpioScorpio maurus palmatus, and has been considered as a cell-penetrating peptide (CPP) for severalyears. MCa presents a therapeutic interest for the intracellular delivery of cargoes, andthis thesis aims to characterise the cell penetration properties of the native molecule as well assome of its variants’.After quantifying several truncated (linear) variants’ internalisation, I have been able tohighlight the fact that all of those analogs possess a higher internalization ability than those ofstandard CPP (especially Tat and penetratin). Among those variants, the analog MCaUF1−9 hasa relatively high rentention time within cells, as well as a slightly increased accumulation whenin an acidic environment (which occurs during solid tumours formation). This new CPP showsa certain therapeutic potential but the study of nativeMCa, remarkably stable in vivo, remainsa priority
Höfs, Sarah [Verfasser], Bernhard Gutachter] Hube, Joachim [Gutachter] Ernst, and Kerstin [Gutachter] [Voigt. "Identification of Candidalysin : a Candida albicans peptide toxin involved in epithelial damage / Sarah Höfs ; Gutachter: Bernhard Hube, Joachim Ernst, Kerstin Voigt." Jena : Friedrich-Schiller-Universität Jena, 2016. http://d-nb.info/1177608758/34.
Повний текст джерелаBernedo-Navarro, Robert Alvin 1975. "Obtenção de peptídeos com capacidade inibitória da ação citotoxigênica das toxinas Stx de Escherichia colia partir de bibliotecas de phage display." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314705.
Повний текст джерелаTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Escherichia coli produtora de toxina de Shiga (STEC) é um grupo de importantes patógenos para humanos. Essas bactérias são relacionadas a várias doenças, como por exemplo, Síndrome Urêmica Hemolítica e produzem potentes toxinas denominadas toxinas de Shiga. Essas toxinas, tanto Stx1 quanto Stx2, compartilham um receptor celular comum, a globotriaosilceramida (Gb3) e exibem a mesma atividade biológica intracelular. O desenvolvimento de novos agentes neutralizantes dos danos induzidos por Stx pode representar uma estratégia promissora para o tratamento das doenças causadas por STEC em humanos. No presente estudo, nós desenvolvemos peptídeos sintéticos que exibem atividade neutralizante contra a citotoxicidade induzida por Stx tanto in vitro quanto in vivo e, além disso, que se ligam eficientemente ao receptor Gb3. O peptídeo P12-26 compete eficientemente com Stx2 para a ligação ao Gb3 in vitro. Além disso, os peptídeos PC7-12, P12-26 e PC7-30 inibiram a citotoxicidade de Stx1 e Stx2 em células Vero. Nós observamos que o peptídeo PC7-30 em forma de loop e o peptídeo P12-26 que é linear produziram as maiores porcentagens de inibição de Stx1 e Stx2 em células Vero, respectivamente. No entanto, o peptídeo P12-26 não inibiu a letalidade em camundongos, enquanto que o peptídeo PC7-30 inibiu a letalidade causada pela toxina Stx1. Nossos resultados indicam que os peptídeos P12-26 e PC7-30 são candidatos promissores para o desenvolvimento de agentes terapêuticos contra as doenças em seres humanos causadas por STEC
Abstract: Shiga toxin-producing Escherichia coli strains are important pathogens for humans. These bacteria are linked with severe diseases such as hemolytic uremic syndrome and produce potent known as Shiga toxins. These toxins, Stx1 and Stx2, share a common cellular receptor called globotriaosylceramide (Gb3) and exhibit the same intracellular biological activity. The development of new neutralizing agents for Stx-induced damage may represent a promising strategy for the treatment of diseases caused by STEC infections. In this study, we developed synthetic peptides that exhibit neutralizing activity against Stxinduced cytotoxicity both in vitro and in vivo and that bind efficiently to the Gb3 receptor. The peptide P12-26 competed efficiently with Stx2 for binding to Gb3 in vitro. Moreover, the peptides PC7-12, P12-26 and PC7-30 inhibited the cytotoxicity of Stx1 and Stx2 in Vero cells. We observed that the loop-constrained peptide PC7-30 and linear peptide P12-26 produced higher percentages of inhibition of Stx1 and Stx2 in Vero cells, respectively. However, the peptide P12-26 did not inhibit lethality in mice, whereas the loopconstrained peptide PC7-30 inhibited the lethality caused by Stx1. Our results indicate that the peptides P12-26 and PC7-30 are promising candidates for the development of therapeutic agents against diseases caused by STEC in humans
Doutorado
Bioquimica
Doutor em Biologia Funcional e Molecular
Arnett, Eusondia A. "Neutrophil products inhibit LLO secretion and activity, and Listeria monocytogenes intracellular growth." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1374064718.
Повний текст джерелаHickey, Ashley N. "Expression of CTB-proinsulin in transgenic chloroplasts." Honors in the Major Thesis, University of Central Florida, 2008. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1088.
Повний текст джерелаBachelors
Burnett College of Biomedical Sciences
Molecular and Microbiology
Marvin, Laure. "Etude de toxines peptidiques du venin de la mygale Scodra griseipes." Rouen, 1997. http://www.theses.fr/1997ROUES016.
Повний текст джерелаMellor, Ian R. "The biophysics of peptide ion channels." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335759.
Повний текст джерелаSt, Pierre Liam Daniel. "Identification and comparative analysis of novel factors from the venom gland of the coastal taipan (Oxyuranus scutellatus) and related species." Thesis, Queensland University of Technology, 2005. https://eprints.qut.edu.au/16677/1/Liam_St_Pierre_Thesis.pdf.
Повний текст джерелаSt, Pierre Liam Daniel. "Identification and comparative analysis of novel factors from the venom gland of the coastal taipan (Oxyuranus scutellatus) and related species." Queensland University of Technology, 2005. http://eprints.qut.edu.au/16677/.
Повний текст джерелаChaivimol, Jittra. "The study of peptide toxins from freshwater cyanobacteria." Thesis, University of Warwick, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389448.
Повний текст джерелаBenites, Thais Azevedo [UNESP]. "Peptídeos sintéticos no estudo do sistema toxina-antitoxina ParE/ParD." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/151105.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O sistema ParE-ParD é um sistema Toxina-Antitoxina (TA) do tipo II (composto por duas proteínas) encontrado no plasmídeo RK2 de uma gama de bactérias. A antitoxina ParD (9kDa) é capaz de neutralizar a citotoxicidade da toxina ParE, pela formação de um complexo estável, e também é eficaz na auto-repressão do operon parDE. A toxina (12kDa) apresenta atividade citotóxica no processo de replicação do DNA por interferir diretamente na ação da DNA girase. Estudos prévios sugeriram que a região C-terminal da antitoxina é responsável pelo processo de interação com ParE. Embora esta toxina possa ser encontrada em um grande número de microrganismos, ainda apresenta mecanismos de citotoxicidade e funções celulares a serem elucidadas. Neste contexto, este trabalho teve como objetivo a tentativa de expressão das duas proteínas ParE e ParD, bem como o design e a síntese de peptídeos análogos da antitoxina, para a realização de estudos de interação molecular, a fim de encontrar uma estrutura mínima de ParD capaz de inativar a função toxica de ParE. Com base nas informações estruturais, obtidas por modelagem e dinâmica molecular, quatro sequências peptídicas análogas de ParD foram projetadas e sintetizadas pela metodologia da fase sólida. As sequências foram analisadas e purificadas por cromatografia líquida de alta eficiência e caracterizadas por espectrometria de massas. Os estudos de interação foram realizados através de ensaios de cromatografia de afinidade e supressão de fluorescência. A fluorescência intrínseca de ParEAC2 foi suprimida pelos análogos de ParD (ParDTB1, ParDTB3, ParDTB5 e ParDTB6), evidenciando a formação de complexos estáveis entre as espécies, resultados confirmados pelos ensaios de cromatografia de afinidade. Resultados semelhantes foram obtidos empregando a proteína ParD obtida por expressão heteróloga. Com base nos resultados obtidos, foi possível concluir que o análogo ParDTB1 representa uma estrutura peptídica mínima com potencial para neutralizar o efeito da toxina ParE.
The ParE-ParD system is a toxin-antitoxin (TA) type II module (composed of two proteins) of the plasmid RK2 of a range of bacteria. The ParD antitoxin (9 kDa) is able to neutralize the cytotoxicity of the ParE toxin by forming a stable complex and is effective in the auto repression of the parDE operon. The toxin (12 kDa) exhibits cytotoxic activity by blocking DNA replication, acting directly in the DNA gyrase action. Previous studies have been suggest that the C-terminal region of the antitoxin is responsible for the interaction process with ParE. Although this toxin can be find in a large number of microorganisms, still have cytotoxicity mechanisms and cellular functions to be elucidate. In this context, this work aimed at the expression of ParE and ParD proteins, as well as the design and synthesis of antitoxin analog peptides, to perform molecular interaction studies in order to find a minimum ParD structure able to inactivate the toxic function of ParE. Based on the structural information obtained by modeling and molecular dynamics, four analogous peptide sequences of ParD were designed and synthesized by the solid phase methodology. The peptide sequences were analyzed and purified by high performance liquid chromatography and characterized by mass spectrometry. Interaction studies were performed by affinity chromatography and fluorescence suppression assays. The intrinsic fluorescence of ParEAC2 was suppressed by ParD analogs (ParDTB1, ParDTB3, ParDTB5 and ParDTB6) addition, evidencing the formation of stable complexes between the species, results confirmed by the affinity chromatography assays. Similar results were obtained using ParD protein obtained by heterologous expression. Based on the results obtained, it was possible to conclude that the ParDTB1 analog represents a minimal peptide structure with potential to neutralize the effect of the ParE toxin.
Fletcher, David Ian. "Synthesis and structure-activity studies of novel potassium ion channel blockers." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265183.
Повний текст джерелаMarcello, Alessandro. "Escherichia coli heat-labile enterotoxin : a multipurpose delivery system for peptides and epitopes." Thesis, University of Kent, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387151.
Повний текст джерелаLi, Feng. "Studies on inhibition against anthrax lethal toxin." Oklahoma City : [s.n.], 2010.
Знайти повний текст джерелаCoyle, Sadie Marie. "Investigations of microcystins (cyanobacterial peptide toxins) : detection, purification and analysis." Thesis, Robert Gordon University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360091.
Повний текст джерелаSouissi, Wided. "Cytocidal activity of Cry41Aa, an anticancer toxin from Bacillus thuringiensis." Thesis, University of Sussex, 2018. http://sro.sussex.ac.uk/id/eprint/80446/.
Повний текст джерелаPatchett, John Colin. "Cellular diversity in Microcystis aeruginosa : implications with respect to peptide toxins." Thesis, University of Warwick, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398715.
Повний текст джерелаMarquet, Fabrice. "Action de la sorbine sur les sécrétions induites par le VIP et la toxine cholérique à différents niveaux de l'intestin chez le rat, in vivo." Lyon 1, 1998. http://www.theses.fr/1998LYO1T222.
Повний текст джерелаBaker, Keren Julie. "Effects of peptide toxins on the Ca'2'+-ATPase of sarcoplasmic reticulum." Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296260.
Повний текст джерелаGöransson, Anna-Lena. "The Alzheimer Aβ Peptide : Identification of Properties Distinctive for Toxic Prefibrillar Species". Licentiate thesis, Linköpings universitet, Molekylär Bioteknik, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-76741.
Повний текст джерелаRippa, Sonia. "Interactions peptaïbols/plantes : étude de l'effet de l'alaméthicine, toxine ou éliciteur de réactions de défense, chez la plante modèle Arabidopsis thaliana." Compiègne, 2007. http://www.theses.fr/2007COMP1688.
Повний текст джерелаPeptaibols are helicoidal amphipathic peptides produced by soil fungi. They form pores allowing the passage of ions through plasmic membranes. Recent work highlighted their elicitor properties in plants. We studied the effect of the peptaibol alamethicin on Arabidopsis thaliana. Moderate concentrations of alamethicin induce physiological effects belonging to the plant hypersensitive response. Higher concentrations are toxic and quickly induce a characteristic ribosomal RNA cleavage. The properties of alamethicin in plants are probably related to its interaction with the plasmic membrane, to the presence of a-aminoisobutyric acid in its sequence and to its resistance to plant proteases. The use of a fluorescent analogue of alamethicin might suggest the existence of a secondary intracellular target
Péré-Védrenne, Christelle. "Etude de la Cytolethal Distending Toxin B des Hélicobacters dans l’inflammation et la carcinogenèse digestive." Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0404/document.
Повний текст джерелаThe demonstration of the role of the Cytolethal Distending Toxin (CDT) of Helicobacter hepaticusin the development of hepatocarcinoma in mice, makes this toxin a relevant candidate in theactivation of precancerous processes. As in the case of the CagA toxin of Helicobacter pylori, theCdtB active subunit of CDT could be an oncoprotein. We studied the role of Helicobacter CdtB ininflammation and digestive carcinogenesis using a lentiviral strategy for constitutive or conditionalexpression of the CdtB subunit or its corresponding DNase mutant. We conducted a study of thetranscriptome and showed that CdtB induced an inflammatory response by overexpressingcytokines, chemokines, antimicrobial peptides and activating the NF-kB pathway in epithelialcells. The CdtB also regulated the expression and nuclear localization of the transcription factorand oncogene MafB. These results were confirmed for the CdtB of Helicobacter pullorum.Infection of cells with wild type strains and the corresponding CDT-mutant strains (of H. hepaticus& H. pullorum) were used to validate the results and to attribute the effects to the CdtB and, inparticular, to its DNase activity. We also developed a novel epithelial cell xenograft model toevaluate the inducible expression of H. hepaticus CdtB. In this model, the CdtB, in addition to itspreviously well-known effects, delayed tumor growth, induced apoptosis, senescence and theoverexpression of nuclear proliferation marker, Ki-67, suggesting cell survival. All of these resultsprovide new arguments in favor of the oncogenic potential of the CDT
Tonk, L. "Impact of environmental factors on toxic and bioactive peptide production by harmful cyanobacteria." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2007. http://dare.uva.nl/document/51378.
Повний текст джерелаPedoussaut, Sylvie. "Immunisation sérique et mucosale contre la toxine cholérique à l'aide de peptides synthétiques : mise en évidence d'un héptapeptide immunogénique en absence de porteur." Paris 5, 1988. http://www.theses.fr/1988PA05P615.
Повний текст джерелаRadzey, Hanna Agnes. "Synthesis of fluorescent toxin and nucleotide derivatives to specifically address membrane proteins." Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2015. http://hdl.handle.net/11858/00-1735-0000-0022-6055-5.
Повний текст джерелаBodles, Angela M. "Studies on physiochemical and toxic properties of peptides implicated in Alzheimer's disease." Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343089.
Повний текст джерелаSerra, Vincent. "Influence de l'association C3b-toxine tétanique sur la production de peptides immunogéniques." Université Joseph Fourier (Grenoble), 1998. http://www.theses.fr/1998GRE10046.
Повний текст джерелаGauckler, Philipp Alexander [Verfasser]. "Identifizierung inhibitorischer Peptide gegen die Toxine von Clostridium difficile aus humanem Hämofiltrat / Philipp Alexander Gauckler." Ulm : Universität Ulm, 2018. http://d-nb.info/1162193549/34.
Повний текст джерелаRocha, Camila Aguiar [UNESP]. "Peptídeos derivados da toxina ParE: síntese, estrutura e estudos de inibição de DNA topoisomerases." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/110373.
Повний текст джерелаO sistema toxina-antitoxina ParE-ParD é um sistema bacteriano de morte póssegregacional codificado numa ampla gama de hospedeiros. ParE é uma proteína pequena, de aproximadamente 12 kDa codificada pelo gene parE. ParD é uma antitoxina de cerca de 9 kDa, codificada pelo gene parD, capaz de complexar com ParE e neutralizá-la. Estudos têm mostrado o envolvimento da enzima DNA girase no processo de morte celular pela ParE, entretanto, não se tem disponível na literatura nenhuma evidência de inibição desta proteína sobre a atividade da topoisomerase IV. Embora encontrada numa ampla diversidade de microorganismos, ParE não possui função celular totalmente elucidada e seu mecanismo de citotoxicidade permanece ainda desconhecido. Com base na estrutura primária da proteína ParE de E. coli e nos escassos dados disponíveis para esta toxina, peptídeos miméticos foram racionalmente projetados visando compreender o mecanismo de inibição de ParE sobre a atividade da DNA girase, bem como, avaliar a ação destes miméticos na atividade da Topoisomerase IV e da Topo II humana. Estas sequências peptídicas foram sintetizadas pela metodologia de fase sólida, purificadas e analisadas por cromatografia líquida de alta eficiência e caracterizadas por espectrometria de massas. A capacidade de inibição destes peptídeos miméticos sobre a atividade das topoisomerases foi testada por ensaios de eletroforese em gel. Os peptídeos que apresentaram melhores resultados de inibição sobre a atividade das topoisomerases foram o ParERM3 e o ParEC3, projetados para conter os resíduos de aminoácidos L61-R100 e L69-R100, respectivamente, presentes na porção C-terminal da estrutura da proteína ParE de Escherichia coli. A sequência “LNIES” (L101 a S105), quando presente nos peptídeos miméticos atenuou a toxicidade dos mesmos frente às topoisomerases, provavelmente por interferir na interação peptídeo-topoisomerase. Embora não existam...
The toxin-antitoxin system ParE-ParD is a bacterial system of post-segregational death encoded in a wide range of hosts. ParE is a small protein of approximately 12 kDa encoded by parE gene. ParD is an antitoxin about 9 kDa, encoded by the parD gene, able of complexing with ParE and neutralize it. Studies have shown the involvement of the enzyme DNA gyrase in the cell death process by ParE, however, is not available in the literature any evidence of inhibition of this protein on the activity of topoisomerase IV. Although found in a wide variety of micro-organisms, the ParE function has not been fully elucidated and its cytotoxic mechanism remains unknown. Based on the primary structure of the E. coli ParE and the limited data available for this toxin, mimetic peptides were rationally designed aiming at understanding the mechanism of inhibition of ParE on the activity of DNA gyrase, as well as on the topoisomerase IV and human topoisomerase II activities. These peptides sequences were synthesized by solid phase methodology, purified and analyzed by high performance liquid chromatography and characterized by mass spectrometry. The ability of these mimetics to inhibit the activity of topoisomerases was tested by electrophoresis on agarose gel. The peptides that showed better results on the inhibition activity of topoisomerases were ParERM3 and ParEC3 , designed to contain the L61-R100 and L69-R100 amino acids sequence, respectively, found of the C-terminal portion of the ParE structure of Escherichia coli. The LNIES sequence (L101 to S105), when present in the mimetic peptides, attenuated the toxicity of the peptides on topoisomerases activity, probably by interfering in the topoisomerase - peptide interactions. Despite the absence of data in the literature regarding the toxicity of ParE protein on the topo IV and human topo II activities, the peptides ParERM3 and ParEC3 showed better inhibitory activity on these enzymes when compared...
Rocha, Camila Aguiar. "Peptídeos derivados da toxina ParE : síntese, estrutura e estudos de inibição de DNA topoisomerases /." Araraquara, 2014. http://hdl.handle.net/11449/110373.
Повний текст джерелаBanca: Saulo Santesso Garrido
Banca: Clóvis Ryuichi Nakaie
Resumo: O sistema toxina-antitoxina ParE-ParD é um sistema bacteriano de morte póssegregacional codificado numa ampla gama de hospedeiros. ParE é uma proteína pequena, de aproximadamente 12 kDa codificada pelo gene parE. ParD é uma antitoxina de cerca de 9 kDa, codificada pelo gene parD, capaz de complexar com ParE e neutralizá-la. Estudos têm mostrado o envolvimento da enzima DNA girase no processo de morte celular pela ParE, entretanto, não se tem disponível na literatura nenhuma evidência de inibição desta proteína sobre a atividade da topoisomerase IV. Embora encontrada numa ampla diversidade de microorganismos, ParE não possui função celular totalmente elucidada e seu mecanismo de citotoxicidade permanece ainda desconhecido. Com base na estrutura primária da proteína ParE de E. coli e nos escassos dados disponíveis para esta toxina, peptídeos miméticos foram racionalmente projetados visando compreender o mecanismo de inibição de ParE sobre a atividade da DNA girase, bem como, avaliar a ação destes miméticos na atividade da Topoisomerase IV e da Topo II humana. Estas sequências peptídicas foram sintetizadas pela metodologia de fase sólida, purificadas e analisadas por cromatografia líquida de alta eficiência e caracterizadas por espectrometria de massas. A capacidade de inibição destes peptídeos miméticos sobre a atividade das topoisomerases foi testada por ensaios de eletroforese em gel. Os peptídeos que apresentaram melhores resultados de inibição sobre a atividade das topoisomerases foram o ParERM3 e o ParEC3, projetados para conter os resíduos de aminoácidos L61-R100 e L69-R100, respectivamente, presentes na porção C-terminal da estrutura da proteína ParE de Escherichia coli. A sequência "LNIES" (L101 a S105), quando presente nos peptídeos miméticos atenuou a toxicidade dos mesmos frente às topoisomerases, provavelmente por interferir na interação peptídeo-topoisomerase. Embora não existam...
Abstract: The toxin-antitoxin system ParE-ParD is a bacterial system of post-segregational death encoded in a wide range of hosts. ParE is a small protein of approximately 12 kDa encoded by parE gene. ParD is an antitoxin about 9 kDa, encoded by the parD gene, able of complexing with ParE and neutralize it. Studies have shown the involvement of the enzyme DNA gyrase in the cell death process by ParE, however, is not available in the literature any evidence of inhibition of this protein on the activity of topoisomerase IV. Although found in a wide variety of micro-organisms, the ParE function has not been fully elucidated and its cytotoxic mechanism remains unknown. Based on the primary structure of the E. coli ParE and the limited data available for this toxin, mimetic peptides were rationally designed aiming at understanding the mechanism of inhibition of ParE on the activity of DNA gyrase, as well as on the topoisomerase IV and human topoisomerase II activities. These peptides sequences were synthesized by solid phase methodology, purified and analyzed by high performance liquid chromatography and characterized by mass spectrometry. The ability of these mimetics to inhibit the activity of topoisomerases was tested by electrophoresis on agarose gel. The peptides that showed better results on the inhibition activity of topoisomerases were ParERM3 and ParEC3 , designed to contain the L61-R100 and L69-R100 amino acids sequence, respectively, found of the C-terminal portion of the ParE structure of Escherichia coli. The "LNIES" sequence (L101 to S105), when present in the mimetic peptides, attenuated the toxicity of the peptides on topoisomerases activity, probably by interfering in the topoisomerase - peptide interactions. Despite the absence of data in the literature regarding the toxicity of ParE protein on the topo IV and human topo II activities, the peptides ParERM3 and ParEC3 showed better inhibitory activity on these enzymes when compared...
Mestre
Benites, Thais Azevedo. "Peptídeos sintéticos no estudo do sistema toxina-antitoxina ParE/ParD /." Araraquara, 2017. http://hdl.handle.net/11449/151105.
Повний текст джерелаBanca: Henrique da Silva
Banca: Luiz Carlos Bertucci Barbosa
Resumo: O sistema ParE-ParD é um sistema Toxina-Antitoxina (TA) do tipo II (composto por duas proteínas) encontrado no plasmídeo RK2 de uma gama de bactérias. A antitoxina ParD (9kDa) é capaz de neutralizar a citotoxicidade da toxina ParE, pela formação de um complexo estável, e também é eficaz na auto-repressão do operon parDE. A toxina (12kDa) apresenta atividade citotóxica no processo de replicação do DNA por interferir diretamente na ação da DNA girase. Estudos prévios sugeriram que a região C-terminal da antitoxina é responsável pelo processo de interação com ParE. Embora esta toxina possa ser encontrada em um grande número de microrganismos, ainda apresenta mecanismos de citotoxicidade e funções celulares a serem elucidadas. Neste contexto, este trabalho teve como objetivo a tentativa de expressão das duas proteínas ParE e ParD, bem como o design e a síntese de peptídeos análogos da antitoxina, para a realização de estudos de interação molecular, a fim de encontrar uma estrutura mínima de ParD capaz de inativar a função toxica de ParE. Com base nas informações estruturais, obtidas por modelagem e dinâmica molecular, quatro sequências peptídicas análogas de ParD foram projetadas e sintetizadas pela metodologia da fase sólida. As sequências foram analisadas e purificadas por cromatografia líquida de alta eficiência e caracterizadas por espectrometria de massas. Os estudos de interação foram realizados através de ensaios de cromatografia de afinidade e supressão de fluorescência. ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The ParE-ParD system is a toxin-antitoxin (TA) type II module (composed of two proteins) of the plasmid RK2 of a range of bacteria. The ParD antitoxin (9 kDa) is able to neutralize the cytotoxicity of the ParE toxin by forming a stable complex and is effective in the auto repression of the parDE operon. The toxin (12 kDa) exhibits cytotoxic activity by blocking DNA replication, acting directly in the DNA gyrase action. Previous studies have been suggest that the C-terminal region of the antitoxin is responsible for the interaction process with ParE. Although this toxin can be find in a large number of microorganisms, still have cytotoxicity mechanisms and cellular functions to be elucidate. In this context, this work aimed at the expression of ParE and ParD proteins, as well as the design and synthesis of antitoxin analog peptides, to perform molecular interaction studies in order to find a minimum ParD structure able to inactivate the toxic function of ParE. Based on the structural information obtained by modeling and molecular dynamics, four analogous peptide sequences of ParD were designed and synthesized by the solid phase methodology. The peptide sequences were analyzed and purified by high performance liquid chromatography and characterized by mass spectrometry. Interaction studies were performed by affinity chromatography and fluorescence suppression assays. The intrinsic fluorescence of ParEAC2 was suppressed by ParD analogs (ParDTB1, ParDTB3, ParDTB5 and ParDTB6) add... (Complete abstract click electronic access below)
Mestre
Monteiro, Sandra Maria Nunes. "Efficacy of glutamine, peptides and vitamins A and E supplementation on diarrheal disease induced by methotrexate and cholera toxin: improvement of intestinal barrier function." Universidade Federal do CearÃ, 2004. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=596.
Повний текст джерелаA desnutriÃÃo, desidrataÃÃo e agentes antineoplÃsicos, tais como o metotrexato (MTX), sÃo imediatos causadores das doenÃas diarrÃicas. Objetivando investigar a mucosite intestinal (MI) induzida por MTX, a eficÃcia das soluÃÃes de reidrataÃÃo oral (SRO) acrescidas com glutamina (Gln), alanilglutamina (Ala-Gln), Hyprol 4107 (HYP) e hyfoama (HYFO) utilizou-se a perfusÃo intestinal. E para a suplementaÃÃo com vitaminas A (VITA) e E (VITE), Gln e peptÃdeos, utilizou-se as avaliaÃÃes morfomÃtricas, metabÃlicas e a de permeabilidade intestinal [(teste lactulose/manitol (L/M)], em camundongos (n=344) e em coelhos (n=72). A mucosite intestinal por MTX (2,75 mg/kg/24h s.c., durante 3 dias) foi validada em camundongos, atravÃs da constataÃÃo do quadro diarrÃico e do prejuÃzo no estado nutricional (-1.89Â0,52 g) estabelecido apÃs o 3o dia de tratamento. A anÃlise morfomÃtrica demonstrou achatamento de vilos (364,8Â19.9 mm) e hiperplasia de criptas (251Â19.2 mm) intestinais com aumento do nÃmero de apoptoses (7.48Â1, 23/cripta), no duodeno e no jejuno. A taxa L/M no grupo MTX foi maior c que no controle (0,35). A perfusÃo intestinal com toxina da cÃlera aumentou a secreÃÃo de Na+ (-12,8Â1.4 mEq/g/min), Cl- (-12,9Â4,6 mEq/g/min) e de Ãgua (-0,02 Â0,04 ml/g/min). As SRO acrescidas de Gln e peptÃdeos, restauram este efeito secretÃrio. A suplementaÃÃo de Gln e peptÃdeos, VITA e VITE, melhoram o ganho ponderal, a ingestÃo de raÃÃo, as alteraÃÃes morfolÃgicas e a apoptose, no modelo de mucosite intestinal. Nenhuma alteraÃÃo foi observada no padrÃo de mitoses nas criptas intestinais, apÃs o 3o dia de tratamento com MTX. A suplementaÃÃo nutricional reduziu na mucosite, a elevaÃÃo das taxas de L/M (0,35 para 0,73) nas vias paracelular e transcelular. Nossos resultados sugerem que, o restabelecimento da barreira morfofuncional, induzido pela suplementaÃÃo, foi obtido atravÃs de um aumento do transporte de cÃtions (Na+ e K+) na mucosa, do fornecimento de substrato energÃtico para o enterÃcito, inibiÃÃo da apoptose (0,25Â0,05), de cÃlulas indiferenciadas incremento no potencial redox e reduÃÃo da peroxidaÃÃo lipÃdica das cÃlulas intestinais diferenciadas. EntÃo sugerimos que o uso de SRO acrescidas de Gln e peptÃdeos podem prevenir a desnutriÃÃo e reduzir as doenÃas diarrÃicas, e a suplementaÃÃo com VITE e VITA melhorar a morfo fisiologia da barreira intestinal
A desnutriÃÃo, desidrataÃÃo e agentes antineoplÃsicos, tais como o metotrexato (MTX), sÃo imediatos causadores das doenÃas diarrÃicas. Objetivando investigar a mucosite intestinal (MI) induzida por MTX, a eficÃcia das soluÃÃes de reidrataÃÃo oral (SRO) acrescidas com glutamina (Gln), alanilglutamina (Ala-Gln), Hyprol 4107 (HYP) e hyfoama (HYFO) utilizou-se a perfusÃo intestinal. E para a suplementaÃÃo com vitaminas A (VITA) e E (VITE), Gln e peptÃdeos, utilizou-se as avaliaÃÃes morfomÃtricas, metabÃlicas e a de permeabilidade intestinal [(teste lactulose/manitol (L/M)], em camundongos (n=344) e em coelhos (n=72). A mucosite intestinal por MTX (2,75 mg/kg/24h s.c., durante 3 dias) foi validada em camundongos, atravÃs da constataÃÃo do quadro diarrÃico e do prejuÃzo no estado nutricional (-1.89Â 0,52 g) estabelecido apÃs o 3o dia de tratamento. A anÃlise morfomÃtrica demonstrou achatamento de vilos (364,8Â 19.9 Âm) e hiperplasia de criptas (251Â 19.2 Âm) intestinais com aumento do nÃmero de apoptoses (7.48Â 1, 23/cripta), no duodeno e no jejuno. A taxa L/M no grupo MTX foi maior c que no controle (0,35). A perfusÃo intestinal com toxina da cÃlera aumentou a secreÃÃo de Na+ (-12,8Â 1.4 ÂEq/g/min), Cl- (-12,9Â 4,6 ÂEq/g/min) e de Ãgua (-0,02 Â 0,04 ml/g/min). As SRO acrescidas de Gln e peptÃdeos, restauram este efeito secretÃrio. A suplementaÃÃo de Gln e peptÃdeos, VITA e VITE, melhoram o ganho ponderal, a ingestÃo de raÃÃo, as alteraÃÃes morfolÃgicas e a apoptose, no modelo de mucosite intestinal. Nenhuma alteraÃÃo foi observada no padrÃo de mitoses nas criptas intestinais, apÃs o 3o dia de tratamento com MTX. A suplementaÃÃo nutricional reduziu na mucosite, a elevaÃÃo das taxas de L/M (0,35 para 0,73) nas vias paracelular e transcelular. Nossos resultados sugerem que, o restabelecimento da barreira morfofuncional, induzido pela suplementaÃÃo, foi obtido atravÃs de um aumento do transporte de cÃtions (Na+ e K+) na mucosa, do fornecimento de substrato energÃtico para o enterÃcito, inibiÃÃo da apoptose (0,25Â 0,05), de cÃlulas indiferenciadas incremento no potencial redox e reduÃÃo da peroxidaÃÃo lipÃdica das cÃlulas intestinais diferenciadas. EntÃo sugerimos que o uso de SRO acrescidas de Gln e peptÃdeos podem prevenir a desnutriÃÃo e reduzir as doenÃas diarrÃicas, e a suplementaÃÃo com VITE e VITA melhorar a morfo fisiologia da barreira intestinal
Porcu, Bernardi Elisabeth. "Cyclotetrapeptides analogues de la chlamydocine et de l'HC-toxine à visée thérapeutique." Montpellier 2, 1991. http://www.theses.fr/1991MON20153.
Повний текст джерелаBarbosa, Luiz Carlos Bertucci [UNESP]. "Peptídeos derivados da toxina bacteriana ParE: síntese, estrutura e ação inibitória sobre a atividade de topoisomerases." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/100731.
Повний текст джерелаConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O sistema ParE-ParD é um sistema toxina-antitoxina bacteriano, sendo ParE a toxina e ParD a antitoxina. ParD é capaz de neutralizar a ação de ParE formando um complexo com o mesmo, o qual é eficaz na autorregulação do operon parDE. Estudos têm mostrado que a atividade tóxica de ParE ocorre inibindo a atividade da DNA girase, mas nenhum efeito desta proteína sobre a atividade da topoisomerase IV foi observado até hoje. Baseando-se na estrutura primária da toxina ParE de Escherichia coli, bem como nos escassos dados em relação a esta toxina, a meta deste trabalho foi a obtenção de peptídeos sintéticos baseados nesta proteína a fim de avaliar as sequências de aminoácidos responsáveis pela interação com as diferentes topoisomerases bacterianas, além de tentar isolar uma sequência polipeptídica com potencial atividade inibitória sobre essas enzimas. Utilizando modelagem molecular por homologia, um modelo tridimensional para toxina ParE de E. coli foi obtido e validado. Com base nos dados estruturais inferidos a partir do modelo da estrutura tridimensional de ParE, 12 peptídeos foram racionalmente desenhados e sintetizados pela metodologia da fase sólida. Ensaios de inibição in vitro da atividade de superenovelamento de DNA pela girase e de relaxamento de DNA pela topoisomerase IV foram realizados e indicaram que os peptídeos ParE3 (ParE 80-100), ParE8 (ParE 61-105), ParE10 (ParE 61-87) e ParE12 (ParE 61-79) atuam como bons inibidores de ambas enzimas. Ensaios de fluorescência intrínseca e anisotropia de fluorescência, empregando peptídeos sintéticos derivados de ParE, evidenciaram que o processo de inibição da atividade da DNA girase pela toxina ParE deve ocorrer por interação com a proteína GyrA da enzima. Foi iniciado neste trabalho os primeiros testes usando lipossomas como veículos...
The operon parDE encode a toxin-antitoxin system formed by ParE toxin and its antitoxin ParD. ParD is able to neutralize ParE action and is effective in autoregulation of the operon. Studies have shown that the toxic activity of the ParE occurs by inhibiting the activity of DNA gyrase, but no effect of this protein on the activity of topoisomerase IV has been observed yet. Based on the primary structure of the Escherichia coli ParE toxin, as well as the scarce data of this toxin, the aim of this work was to obtain synthetic peptides based on this protein in order to assess the amino acid sequences responsible for interaction with the bacterial topoisomerases, besides trying to isolate a polypeptide sequence with potential inhibitory activity against these enzymes. Using molecular homology modeling, a three-dimensional model for E. coli ParE toxin was obtained and validated. Based on structural data inferred from ParE threedimensional model, 12 peptides were rationally designed and synthesized by solid-phase method. Tests of inhibition of the supercoiling reaction of the DNA gyrase and inhibition of DNA relaxation by topoisomerase IV were performed and indicated that the peptides ParE3 (ParE 80-100), ParE8 (ParE 61-105), ParE10 (ParE 61 -87) and ParE12 (ParE 61-79) act as good inhibitors of both enzymes. Intrinsic fluorescence and fluorescence anisotropy assays, using synthetic peptides derived from ParE showed that inhibition process of activity of the DNA gyrase by ParE toxin must occur by interaction with the GyrA protein. In this work was started the first tests using liposomes as carrier vehicles for bioactive peptides derived from ParE. The peptides were efficiently encapsulated in soybean phosphatidyl choline liposomes. It was observed, although reduced, inhibition of bacterial growth when peptides encapsulated in liposomes were... (Complete abstract click electronic access below)
Barbosa, Luiz Carlos Bertucci. "Peptídeos derivados da toxina bacteriana ParE : síntese, estrutura e ação inibitória sobre a atividade de topoisomerases /." Araraquara, 2012. http://hdl.handle.net/11449/100731.
Повний текст джерелаBanca: Eduardo Maffud Cilli
Banca: Wilton Rogério Lustri
Banca: Vani Xavier de Oliveira Junior
Banca: Herida Regina Nunes Salgado
Resumo: O sistema ParE-ParD é um sistema toxina-antitoxina bacteriano, sendo ParE a toxina e ParD a antitoxina. ParD é capaz de neutralizar a ação de ParE formando um complexo com o mesmo, o qual é eficaz na autorregulação do operon parDE. Estudos têm mostrado que a atividade tóxica de ParE ocorre inibindo a atividade da DNA girase, mas nenhum efeito desta proteína sobre a atividade da topoisomerase IV foi observado até hoje. Baseando-se na estrutura primária da toxina ParE de Escherichia coli, bem como nos escassos dados em relação a esta toxina, a meta deste trabalho foi a obtenção de peptídeos sintéticos baseados nesta proteína a fim de avaliar as sequências de aminoácidos responsáveis pela interação com as diferentes topoisomerases bacterianas, além de tentar isolar uma sequência polipeptídica com potencial atividade inibitória sobre essas enzimas. Utilizando modelagem molecular por homologia, um modelo tridimensional para toxina ParE de E. coli foi obtido e validado. Com base nos dados estruturais inferidos a partir do modelo da estrutura tridimensional de ParE, 12 peptídeos foram racionalmente desenhados e sintetizados pela metodologia da fase sólida. Ensaios de inibição in vitro da atividade de superenovelamento de DNA pela girase e de relaxamento de DNA pela topoisomerase IV foram realizados e indicaram que os peptídeos ParE3 (ParE 80-100), ParE8 (ParE 61-105), ParE10 (ParE 61-87) e ParE12 (ParE 61-79) atuam como bons inibidores de ambas enzimas. Ensaios de fluorescência intrínseca e anisotropia de fluorescência, empregando peptídeos sintéticos derivados de ParE, evidenciaram que o processo de inibição da atividade da DNA girase pela toxina ParE deve ocorrer por interação com a proteína GyrA da enzima. Foi iniciado neste trabalho os primeiros testes usando lipossomas como veículos... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The operon parDE encode a toxin-antitoxin system formed by ParE toxin and its antitoxin ParD. ParD is able to neutralize ParE action and is effective in autoregulation of the operon. Studies have shown that the toxic activity of the ParE occurs by inhibiting the activity of DNA gyrase, but no effect of this protein on the activity of topoisomerase IV has been observed yet. Based on the primary structure of the Escherichia coli ParE toxin, as well as the scarce data of this toxin, the aim of this work was to obtain synthetic peptides based on this protein in order to assess the amino acid sequences responsible for interaction with the bacterial topoisomerases, besides trying to isolate a polypeptide sequence with potential inhibitory activity against these enzymes. Using molecular homology modeling, a three-dimensional model for E. coli ParE toxin was obtained and validated. Based on structural data inferred from ParE threedimensional model, 12 peptides were rationally designed and synthesized by solid-phase method. Tests of inhibition of the supercoiling reaction of the DNA gyrase and inhibition of DNA relaxation by topoisomerase IV were performed and indicated that the peptides ParE3 (ParE 80-100), ParE8 (ParE 61-105), ParE10 (ParE 61 -87) and ParE12 (ParE 61-79) act as good inhibitors of both enzymes. Intrinsic fluorescence and fluorescence anisotropy assays, using synthetic peptides derived from ParE showed that inhibition process of activity of the DNA gyrase by ParE toxin must occur by interaction with the GyrA protein. In this work was started the first tests using liposomes as carrier vehicles for bioactive peptides derived from ParE. The peptides were efficiently encapsulated in soybean phosphatidyl choline liposomes. It was observed, although reduced, inhibition of bacterial growth when peptides encapsulated in liposomes were... (Complete abstract click electronic access below)
Doutor
Nash, Ian Alun. "The development of solid phase strategies and methodologies : the synthesis of polyamine toxins and peptide nucleic acids." Thesis, University of Nottingham, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321373.
Повний текст джерелаBoitel, Brigitte. "La reconnaissance T d'un peptide de la toxine tétanique présenté par la molécule de classe II HLA-DR : illustration des bases moléculaires des intéractions TCRαβ / peptide / CMH". Paris 6, 1993. http://www.theses.fr/1993PA066726.
Повний текст джерелаCampos, Lucélia de Almeida. "Isolamento e caracterização da delta toxina do veneno de Crotalus durissus terrificus." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/85/85131/tde-14052012-135435/.
Повний текст джерелаThe Crotalus durissus terrificus venom has been so far described as being of low complexity, with four major components described: convulxin, gyroxin, crotoxin and crotamine. In recent studies, other components of this venom were characterized as, for example, an analgesic factor. In 1980, Vital Brazil predicted the existence of a toxin which could be involved in platelet aggregation, and named it delta toxin. However, this toxin has never been isolated or characterized. The aim of the present work was to purify and characterize this toxin. After FPLC size exclusion chromatography followed by reverse phase HPLC, an homogeneous fraction was obtained, with a molecular weight of 14,074.92 Da. When analyzed by SOS-PAGE, this toxin presented an anomalous behavior, with a molecular weight of 14 kDa, while in 2D gels, spots around 40 kDa and with an isoelectrical point between 4 and 5 were observed suggesting isoforms with glicosilation microheterogeneity. After trypsin digestion, the fragments were submitted to the swissprot databank showing high homology (43% coverage, 15 matching peptides) with trocarin, a prothrombin activator from Tropidechis carinatus. These data were further confirmed by aminoacid analysis. The toxin was tested for its ability to activate factor II and X using synthetic substrates. Our data indicate a direct activation of factor X. The same toxin also behaved as a potent direct platelet aggregation activator on washed platelets. Assays with specific inhibitors indicate that neither metalloproteinase, nor serinoproteinase or t lectin domains are involved in the aggregating activity, since EDTA, benzamidin and D-galactose did not inhibit the toxin. In the present work, we were able to identify, purify and characterize a new toxin from the brazilian rattlesnake. It behaved as predicted by Vital-Brazil and displayed direct factor X activating properties, also inducing platelet aggregation, even at low concentrations. Our data also indicate that it is probably a homotrimer with the subunities linked by hydrophobic and/or electrostatic interactions.
Elgar, Dale. "Ion selectivity and membrane potential effects of two scorpion pore-forming peptides / D. Elgar." Thesis, North-West University, 2005. http://hdl.handle.net/10394/991.
Повний текст джерелаThesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2006.
Cardoso, Kiara Carolina 1979. "Transcriptoma da glândula venenífera da serpente Bothrops alternatus (urutu) e caracterização molecular e bioquímica parcial da dipeptidilpeptidase IV." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312156.
Повний текст джерелаTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: O estudo do transcriptoma de bibliotecas de cDNA da glândula venenífera de serpentes, realizado a partir da análise de ESTs (expressed sequence tags), tem se mostrado útil na identificação de genes expressos neste tecido, inclusive no gênero Bothrops, responsável pela maioria dos acidentes ofídicos no Brasil. Neste trabalho utilizamos uma abordagem transcriptômica para analisar a composição gênica da glândula venenífera da serpente Bothrops alternatus, uma espécie encontrada no sudeste e sul do Brasil, Uruguai, norte da Argentina e leste do Paraguai. Também clonamos e caracterizamos parcialmente a enzima dipeptidilpeptidase IV (DPP IV), uma enzima que cliva peptídeos com prolina ou alanina na penúltima posição em sua porção N-terminal e que tem sido detectada em diversas peçonhas ofídicas. A construção de bibliotecas de cDNA usando métodos convencionais de clonagem, sequenciamento e análise bioinformática resultou em 5,350 ESTs que foram reunidas em 838 contigs and 4512 singletons. Pesquisas a partir de bancos de dados relevantes (BLAST) mostraram 30% de hits e 70% no-hits. Os transcritos relacionados a toxinas correspondem a 23% do total de transcritos e 78% dos hits, respectivamente. A análise por ontologia gênica (GO) detectou genes relacionados ao metabolismo geral, transcrição, tradução, processamento, degradação de polipeptídeos, funções estruturais, e regulação celular. Os principais grupos de toxinas identificados foram metaloproteinases (81%), peptídeos potenciadores da bradicinina/peptídeos natriuréticos do tipo C (8,8%), fosfolipases 'A IND. 2' ('PLA IND. 2'; 5,6%), serinoproteinases (1.9%) e lectinas do tipo C (1,5%). As metaloproteinases eram quase queexclusivamente da classe PIII, com poucas da classe PII e nenhuma da classe PI. As 'PLA IND. 2' eram todas ácidas; nenhuma 'PLA IND. 2' básica foi detectada. Outras toxinas encontradas incluíram a L-aminoácido oxidase, proteínas secretadas ricas em cisteína, DPP IV, hialuronidase, toxinas three-finger e ohanina. Foram identificadas duas proteínas não-tóxicas, a tioredoxina e a Dusp6 (fosfatase de dupla especificidade) que mostraram alto grau de similaridade a proteínas semelhantes de outras serpentes. Também foram observados polimorfismos de nucleotídeos únicos (SNPs - single-nucleotide polymorphisms), microssatélites, transposons e repetições invertidas, todos os quais podem contribuir de alguma forma para a multiplicidade de toxinas na glândula. Estes resultados mostram que a glândula venenífera de B. alternatus possui as principais classes de toxinas encontradas em estudos transcriptômicos e proteômicos de outras espécies botrópicas. ... Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital
Abstract: Transcriptomic studies of snake venom gland cDNA based on the analysis of expressed sequence tags (ESTs) have been useful in identifying the genes expressed in this organ in a variety of species, including the genus Bothrops, which is responsible for most venomous snakebites in Brazil. In this work, we used a transcriptomic approach to analyze the gene composition of the venom gland of Bothrops alternatus (urutu), a species found in southeastern and southern Brazil, Uruguay, northern Argentina e eastern Paraguay. We also cloned and partially characterized dipeptidylpeptidase IV (DPP IV), an enzyme that cleaves peptides with proline or alanine as the penultimate residue in the N-terminal region and has been identified in several snake venoms. A cDNA library constructed using conventional methods of cloning, sequencing and bioinformatic analysis yielded 5,350 ESTs that formed 838 contigs and 4512 singletons. Databank BLAST searches yielded 30% hits and 70% no-hits. Toxin-related transcripts accounted for 23% of the total transcripts and 78% of the hits. Gene ontology analysis detected genes related to general metabolism, transcription, translation, processing, polypeptide degradation, structural functions and cellular regulation. The main toxin groups identified were metalloproteinases (81%), bradykinin-potentiating peptides/C-type natriuretic peptides (8.8%), phospholipases 'A IND. 2' ('PLA IND. 2'; 5.6%), serine proteinases (1.9%) and C-type lectins (1.5%). Metalloproteinases were almost exclusively class PIII, with few class PII and no class PI enzymes. The 'PLA IND. 2' were all acidic; no basic 'PLA IND. 2' were detected. Other toxins identified included L-amino acid oxidase, cysteine-rich secretory proteins, DPP IV, hyaluronidase, three-finger toxins and ohanin. Two non-toxic proteins, thioredoxin and a dual specificity phosphatase (Dusp6), shared high sequence homology with similar proteins from other snakes. Single-nucleotide polymorphisms (SNPs), microsatellites, transposons and inverted repeats were also observed and may contribute to the toxin diversity of the gland. These results show that the venom gland of B. alternatus contains the major toxin classes identified in transcriptomic and proteomic studies of other Bothrops species. The predominance of class PIII metalloproteinases agrees with the hemorrhagic activity of this venom, while the low content of serine proteinases and C-type lectins could account for the less intense coagulopathy observed after envenoming by this species. The lack of basic 'PLA IND. 2' agrees with the lower myotoxicity of this venom compared to other Bothrops species. ... Note: The complete abstract is available with the full electronic digital thesis or dissertations
Doutorado
Farmacologia
Doutor em Farmacologia
Jin, Sha. "Membrane interaction of amyloid–beta (1–42) peptide induces membrane remodeling and benefits the conversion of non–toxic Aβ species into cytotoxic aggregate". Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17632.
Повний текст джерелаThe accumulation of Amyloid beta peptide 1-42 (Ab42) in extracellular plaques is one of the pathological hallmarks of Alzheimer’s disease. Several studies have suggested that a cellular reuptake of Ab42 may be a crucial step in its cytotoxicity, but mechanisms of Ab-membrane interaction and subsequent cellular uptake are not yet understood. The first aim of the present study is to answer the question whether aggregate formation is a prerequisite or a consequence of Ab-membrane interaction and of Ab endocytosis. We visualized aggregate formation of fluorescently labeled Ab42 by Förster resonance energy transfer and tracked its internalization by human neuroblastoma cells. Both monomeric and aggregated Ab42 entered the cells, however, monomer uptake faced a concentration threshold and occurred only at concentrations and time scales that allowed beta-sheet-rich (bS) aggregates to form. By uncoupling membrane binding from internalization, we found that Ab42 monomers as well as small aggregate species bound rapidly to the plasma membrane and formed bS aggregates. These structures were subsequently taken up and accumulated in endocytic vesicles. This process correlated with inhibition of cellular metabolism activities. Our data therefore imply that the formation of bS aggregates at the cell membrane is a prerequisite for Ab42 uptake and cytotoxicity. The second aim of the study is to investigate the Ab-membrane interaction in vitro by using giant unilamellar vesicles and giant plasma membrane vesicles as model membrane systems. We found that both Ab isoforms, Ab42 and Ab40, interacted with the liquid disordered phase of model membranes. Early aggregation intermediates, which did not yet bind to the amyloiddophilic dye Thioflavin T, induced negative membrane curvature. The ability of Ab to induce membrane deformation suggests that Ab may facilitate its own endocytosis. It also hints at a possible physiological function of non-toxic Ab aggregate species.
Quercini, Leila. "The antimicrobial peptide SET-M33. Characterization of back-up molecules for the setup of novel antibiotics and development of a medical device for removing bacterial toxins from blood." Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1070198.
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