Tesis sobre el tema "Phae display"
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De, Leon Ellen Jane Biotechnology & Biomolecular Sciences Faculty of Science UNSW. "Engineering antibodies against complex platelet antigens using phage display technology". Awarded by:University of New South Wales, 2007. http://handle.unsw.edu.au/1959.4/37009.
Texto completoNangola, Sawitree. "The interference of human immunodeficiency virus assembly and maturation by ankyrin repeat proteins". Thesis, Paris 11, 2011. http://www.theses.fr/2011PA112044.
Texto completoPresently, the standard regimen for antiretroviral treatment is highly active antiretroviral therapy (HAART). However, this strategy inherits the well-known side effects and is prone to promote the HIV drug-resistant strains. As a consequence, gene therapy has been introduced as an alternative approach. In this study, we aimed to discover the novel protein-based agents for intervening viral replication by gene targeting procedure. Regarding the efficient folding dynamic in cytoplasm, ankyrin repeat protein was considered to be a candidate scaffold. Several engineered ankyrin binders specific to HIV MA-CA domain were successfully retrieved from the ankyrin-displayed phage library. Three positive clones with high binding activity by ELISA were selected for further analyzing their binding property in soluble form. The best binder, 1D4, recognized its epitope located on CA domain as shown by Western immunobloting and ELISA. The affinity of 1D4 against H6MA-CA was 0.45 μM with one to two moles of target molecule determined by isothermal titration calorimetry (ITC). Although 1D4 exhibited no effect on viral maturation as verified by an ELISA based HIV protease assay technique, it disturbed the viral assembly process in Sup-T1 cells which stably expressed the myristoylated 1D4. This finding has provided a concrete prospect for HIV life cycle interruption by stem cell gene therapy in the future
Rosander, Anna. "Novel applications of shotgun phage display /". Uppsala : Dept. of Microbiology, Swedish Univ. of Agricultural Sciences, 2004. http://epsilon.slu.se/a450.pdf.
Texto completoHolmes, David Ian Roderick. "Phage display of chymotrypsin inhibitor II". Thesis, Imperial College London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283414.
Texto completoSmith, Mathew Wayne. "Phage display and experimental brain therapeutics". Thesis, Cardiff University, 2009. http://orca.cf.ac.uk/55853/.
Texto completoDrever, Matthew. "Generating microcystin antibodies by phage display". Thesis, University of Aberdeen, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445137.
Texto completoMeyer, Scott C. "Non-Covalent Selection Methodologies Utilizing Phage Display". Diss., The University of Arizona, 2007. http://hdl.handle.net/10150/194059.
Texto completoBonnert, Timothy Peter. "Strategies for making antibodies by phage display". Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294402.
Texto completoChing, Ana Tung Ching. "Identificação de adesinas bacterianas por phage display". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-05022013-084410/.
Texto completoLeptospirosis is a worldwide important zoonosis caused by bacteria of the genus Leptospira. In Brazil, most cases is caused by L. interrogans serovar Copenhageni. Our goal was to identify leptospiras adhesins by phage display technique. Libraries of genomic fragments resulted in the identification of ligands with affinity for leptospiras hamster tissues. Screening these libraries against heparan sulfate proteoglycan (HSPG) identified the proteins LigA and LigB. Recombinant proteins were produced and subjected to binding to mammalian cells and extracellular matrix components. LigB recombinant was able to bind to HSPG, heparin and mammalian cells. HSPG and heparin were able to significantly reduce the interaction of this protein with cells. These results highlight the role of leptospiras proteins in its interaction with the host and illustrate the possibility of the use of phage display technique to identify potential adhesins.
Gomes, Margarida. "Développement de bibliothèques de protéines artificielles permettant la création d’outils de reconnaissance moléculaire innovants". Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS030.
Texto completoHere new methods to build a library of artificial proteins based on a new protein framework have been developed. The objective is to generate a source of artificial biodiversity allowing the creation of new interaction capacities with various specific targets. A first-generation library was previously built with this scaffold, but it needed to be optimized. The first step was to explore the reasons of the instability of the first generation proteins library through an in silico approaches followed by a site-directed mutagenesis strategy. The second step was to reduce the number of diversified positions and simplify the randomization scheme of the variants of the library. Then a method of filtering and shuffling of the variants of the bank was elaborated. To increase the proportion of correct coding sequences, a new filtration strategy based on the phage display technique has been developed, exploiting the fact that the scaffold of the librarie. This scaffold has a particularly interesting biological partner able to interact on the "constant" zone. This filtration made it possible to recover a set of well-folded clones. Then, DNA sequences corresponding to these clones were recombined with each other to recreate a greater useful diversity. An optimized library of 2.8 x 108 independent proteins was obtained. This new optimized library has enabled us to select, by a phage display approach, binders against several targets of different structures. These new binders are specific for their targets and have affinities in the μM range. A high throughput sequencing (NGS) approach was also undertaken to further analyse the library sequences and the selection process. This approach offers a new dimension for the characterization of the library built in the laboratory, especially concerning it actual diversity. To follow the selections, we have considered the NGS as a way to identify the target-specific binders through exhaustive analysis of the sequences obtained from selections. The objective here is to develop a general protocol using the NGS approach to identify specific binders isolated by Phage Display
Wright, Michael John. "Anti-tumour chelating recombinant antibodies by phage display". Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405798.
Texto completoMadeja, Benjamin [Verfasser]. "Phage Display Screening for Cement Systems / Benjamin Madeja". Konstanz : KOPS Universität Konstanz, 2018. http://d-nb.info/1202440800/34.
Texto completoDueñas, Marta. "Phage display and bacterial expression of antibody fragments". Lund : Dept. of Immunotechnology, Lund University, 1995. http://catalog.hathitrust.org/api/volumes/oclc/38164515.html.
Texto completoGomes, Carlos Henrique Rodrigues. "Construção de uma bibilioteca de anticorpos ScFv dirigidos contra o fator de crescimento vascular (VEGF)". Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-09082013-093807/.
Texto completoAngiogenesis is the formation of new blood vessels from pre-existing ones and is an important physiological process, which in adults is mostly restricted to wound healing or the female reproductive cycle. However, different illnesses, such as cancer or retinopathies, induce the formation of pathological angiogenesis, necessary for disease progression. Monoclonal antibodies are one of the fastest growing class of biopharmaceuticals with important implications in angiogenesis dependent diseases. Among various methods for the identification of monoclonal antibodies against therapeutic targets is phage display technology. Because the vascular endothelial growth factor (VEGF) is the main molecular factor responsible for the formation of new blood vessels, the major anti-angiogenic drug available in the clinic today is a monoclonal antibody (bevacizumab) directed against VEGF. However, although anti-VEGF therapies are effective, they are not yet ideal due to undesirable side effects and drug resistance. Novel alternatives are necessary to improve on angiogenic therapies. The aim of our study is to identify novel molecular targets and to develop new therapeutic agents for angiogenic dependent diseases. To achieve our goal we have chosen the phage display system in order to select for antibodies with angiogenic properties. An antibody phage library has been developed in our laboratory, directed against VEGF molecule, particularly one of it isoforms. The animals were immunized and developed specific antibodies, detected by ELISA and Western-blot. Amplification of the pool of light and heavy chain Ig genes was performed to produce the single chain (ScFv) fragments for library construction. The ScFv antibody display libraries will be then screened in angiogenic settings to isolate antibodies against specific VEGF isoforms and novel cell surface molecular markers expressed by activated human endothelial cells
Mathonet, Pascale. "Création d'un site allostérique dans la beta-lactamase TEM-1 par évolution dirigée". Université catholique de Louvain, 2004. http://edoc.bib.ucl.ac.be:81/ETD-db/collection/available/BelnUcetd-04282004-121335/.
Texto completoMurarasu, Thomas. "The Shiga Toxin B-Subunit : a Promising Scaffold for the Targeting of Tumor Specific Glycosphingolipids". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS512.
Texto completoCancer is the second cause of death worldwide. Recent advance in cancer treatments involved the identification of cancer biomarkers and the development of efficient therapeutic products able to specifically recognize them. This new class of products has the ability to specifically target tumor cells, with the major advantages to decrease or abolish treatments side effects and relapses of the disease. Unfortunately, a certain number of patients do not respond to those treatments lacking the expression of those biomarkers on their tumor. This project aims at developing new targeted therapies by exploiting a new class of cancer biomarkers, which would potentially extend the therapeutics options against cancer
Wilson, Daniel Ross. "Multivalent pIII phage display libraries, selected issues and applications". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq25187.pdf.
Texto completoYeoh, Tsin Inn Louisa. "Single-chain antibody engineering against mecoprop using phage display". Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.429362.
Texto completoBell, Matthew John. "Phage display of a cDNA library from Arabidopsis thaliana". Thesis, Coventry University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393652.
Texto completoChen, Kuan Ming. "Submillisecond-response blue phase liquid crystals for display applications". Doctoral diss., University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5158.
Texto completoID: 031001409; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Title from PDF title page (viewed June 12, 2013).; Thesis (Ph.D.)--University of Central Florida, 2012.; Includes bibliographical references (p. 82-89).
Ph.D.
Doctorate
Optics and Photonics
Optics and Photonics
Optics
Kelly, Michael A. "Developing Peptide Probes for Membrane Lipids via Phage Display:". Thesis, Boston College, 2020. http://hdl.handle.net/2345/bc-ir:108919.
Texto completoLipid reporters are key signaling molecules in a number of biological processes ranging from apoptosis in mammalian cells to novel resistance mechanisms in pathogenic bacteria. Developing probes to target these lipids is a worthy endeavor, especially when better reporters could mean lives saved. This is particularly true considering new antibiotic resistant pathogens emerge every year with evolving lipid compositions. To combat these pathogens and prevent a potential global pandemic, it is imperative to continue the development of novel and innovative probes/drugs to meet this daunting challenge. To fulfill this demand, we must continue to establish new strategies, enhance current technologies and advance scientific understanding. Only by pushing the boundaries of what is currently possible will we remain one step ahead of these diseases. Diseases like mcr-1 positive bacteria, first documented in 2016, remain largely uncontested. Herein, we seek to expand the available probes specific to key lipid reporters for phosphatidylserine, lysyl-phosphatidylglycerol, and phosphoethanolamine lipid A. Cyclic phage libraries were first utilized to target phosphatidylserine, ultimately producing weak binders. Refining our phage display libraries to include reversible covalent warheads allowed for the identification of more potent lipid reporters. In doing so, we have created the tools necessary to interrogate the unique resistance mechanisms expressed by these drug-resistant pathogens. A strong correlation was observed between peptides binding mcr-1 positive strains, LPS modification on the surface of these bacteria, and level of colistin resistance. To our knowledge, these peptides are the only probes capable of demonstrating this correlation. We surmise that the methods discussed here will pave the way for better diagnostic tools for these resistant pathogens. A recurring method of resistance among gram-positive and gram-negative bacteria has been to decorate their surface with positive amines to repel cationic antimicrobial peptides. As such, our current APBA library and the libraries in development in the Gao lab would be ideally suited to target these and other undiscovered resistance mechanisms
Thesis (PhD) — Boston College, 2020
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
Filipovic, Nedim. "Phage display to identify functional resistance mutations to Rigosertib". Scholarship @ Claremont, 2017. http://scholarship.claremont.edu/cmc_theses/1475.
Texto completoJohansson, Louise. "Proteomic peptide phage display of syntenin-1 and scribble". Thesis, Uppsala universitet, Institutionen för kemi - BMC, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-255887.
Texto completoScott, Nathan. "Anti-tetanus toxin chelating recombinant antibodies by phage display". Thesis, Imperial College London, 2008. http://hdl.handle.net/10044/1/4638.
Texto completoTomini, Khaled. "The isolation of novel leptin variants using phage display". Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/12363/.
Texto completoMagalhães, Leila da Silva. "Importância do domínio extracelular do receptor tirosina quinase Tie1 na angiogênese". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-11042017-081713/.
Texto completoTie1 is a tyrosine kinase receptor expressed by endothelial cells and important in angiogenesis, the formation of new blood vessels from pre-existing ones. This receptor belongs to a small family of receptors composed of two members only (Tie1 and Tie2) to which angiopoietins have been identified as ligands for Tie2. On the other hand, Tie1 is still an orphan receptor with no ligand identified to date. Thus, it is difficult to assess Tie1 mechanism of action in neovascularization without a known ligand. Nevertheless, gene deletion studies have shown that Tie1 is essential in angiogenesis, and plays an important role in retinal and tumoral vascularization. The aim of our study was to evaluate the participation of Tie1 extracellular domain in angiogenesis, and in the process, to identify putative ligands for this receptor. Utilizing phage display, we have identified and characterized a Tie1 specific and selective ligand peptide, which suggests the existence of a binding site unique to this receptor and not shared by other family members. We show that this peptide prevents endothelial cells proliferation, induced by angiopoetin-1, a ligand for Tie2 but which also modulates Tie1 activity. Using a well-accepted mouse model for human diseases, the oxygen induced retinopathy model, we show that this peptide inhibits angiogenesis in vivo. Since this peptide maps to a unique binding site in Tie1, we hypothesized that it might mimic a natural ligand for this receptor. To identify them, proteins with cross reactive epitopes with an anti-peptide sera were identified by proteomic approaches. These proteins are thus possible ligands for Tie1. In summary, we have shown that Tie1 extracellular domain is important in angiogenesis and we have identified putative ligand for this receptor, which might contribute to a better understanding of the molecular mechanisms associated with Tie1 in blood vessel formation. The peptide here characterized may also be an important tool for the development of novel anti-angiogenesis therapeutic approaches for disesase with an angiogenic component.
Lima, Swiany Silveira. "Identificação de adesinas de Leptospira interrogans por shotgun phage display". Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-02052013-095417/.
Texto completoIn Leptospira interrogans, proteins capable to bind to extracellular matrix components have been identified and most of them are important virulence factors. Phage display is a powerful technique to identify new ligands, including adhesin molecules that are important in the first stage of host infection. A shotgun phage display technique was used in order to obtain cell ligands. Four libraries were constructed by inserting random fragments obtained by sonication of L. interrogans DNA into phagemids pG8SAET (BBT1 and BBT2) and pG3DSS (BBT5 and BBT6). The libraries BBT1 and BBT5 contain larger inserts and BBT2 and BBT6 contain smaller inserts, with 1500 bp and 350 bp average sizes, respectively. After panning of BBT5 against mammalian cells and bovine fetal serum, the sequences of selected clones were analyzed for correct orientation and fusion with pIII protein. The proteins encoded by genes LIC11719, LIC10769, LIC13143 and LIC12976 were selected. The genes LIC12976, LIC10768, LIC10769 and LIC13418 were evaluated for their conservation in different pathogenic serovars of L. interrogans and free-living L. biflexa serovar Patoc. Proteins LIC12976 (selected by phage display technique) and also LIC13418 that was selected by bioinformatic tools, were amplified by PCR, cloned into pGEM T easy, subcloned into expression vector pAE and expressed in cellular fraction corresponding to the inclusion body in E. coli BL21 (DE3) Star pLysS and E. coli BL21 SI, respectively. After protein renaturation protocol and purification by affinity chromatography, a group of five BALB/c mice was immunized with the purified proteins. Both proteins were shown to be immunogenic with 1:256000 and 1:512000 polyclonal sera titers, respectively. In Western blot the sera were specific to recognize recombinant proteins and native proteins were detected in pathogenic L. interrogans serovars extracts. In binding assays, recombinant proteins bind to A31, LLC-PK1 and Vero cells and specifically to laminin. In interference cell assay using laminin there was an increase of recombinant protein bindings, which can be explained by the laminin binding to cells and further binding of the recombinant LICs. In cellular localization assay using immunofluorescence and electron microscopy, it was observed that both are surface proteins of L. interrogans. In the animal challenge, the LIC12976 and LIC13418 were not protective. As a whole, this work contributed to the identification of LIC12976 and LIC13418 as new adhesins and they can participate in the virulence of pathogenic Leptospira in the first stage of host pathogen interaction.
Kioshima, Érika Seki [UNIFESP]. "Caracterização de marcadores de virulência em Paracoccidioides brasiliensis". Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/9171.
Texto completoFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A paracoccidioidomicose (PCM) é uma doença sistêmica de caráter granulomatoso, prevalente na América do Sul, causada pelo fungo termodimórfico Paracoccidioides brasiliensis. O fungo apresenta estrutura complexa de proteínas e glicoproteínas e dentre esses componentes, alguns estão envolvidos na patogenicidade da doença. A recuperação da virulência de isolados por meio de passagem in vivo foi realizada com sucesso em nosso laboratório. Os isolados Pb18 atenuado e virulento foram analisados sob diversos ângulos para confirmação dessa modificação. Os resultados de curva de sobrevida, recuperação de CFU de órgão e histologia, mostraram claramente as diferenças no padrão de patogenicidade desses dois isolados. Outras características também foram avaliadas como morfometria, padrão de crescimento e ultraestrutura celular. Análises de expressão gênica diferencial apontaram um perfil de regulação positiva para genes relacionados ao metabolismo de proteínas, de lipídeos e aminoácidos. Algumas moléculas anteriormente descritas como putativos fatores de virulência foram moduladas positivamante, entre as quais podemos citar a calmodulina, proteína kex-like e hsp70. Entretanto, ainda pouco se sabe sobre estes fatores virulência para maioria dos fungos dimórficos, entre eles o P.brasiliensis. Várias técnicas têm sido utilizadas, sem sucesso, para caracterização destas moléculas. Utilizando a metodologia de Phage display, foram selecionados três fagos que se ligam preferencialmente ao isolado Pb18 virulento. Por meio de ensaio de ligação, o fago p04 foi capaz de distinguir graus de virulência de outros quatro isolados. As imagens obtidas por microscopia confocal mostraram que o pep04, acoplado a 6-FAM, foi internalizado somente por leveduras do isolado virulento. Imagens seriadas indicam marcação do meio intracelular, frequentemente associada ou co-localizada à marcação por DAPI. Estes resultados demonstraram que ambos, pep04 e p04, podem ser considerados biomarcadores de virulência na PCM. Para avaliar as consequências das interações destes biomarcadores com células fúngicas, foram realizados ensaios in vitro e in vivo. O fago p04 foi suficiente para impedir a implantação e disseminação do fungo. Além disso, foi capaz de reduzir o número de CFUs recuperadas de animais tratados com este fago, quando comparado ao controle (fago sem inserto). Experimentos in vitro utilizando o pep04 demostraram a atividade fungicida deste peptídeo contra, apenas, o isolado virulento. Desta foram, estes biomarcadores poderão ser utilizados tanto no diagnóstico, quanto na pratica clínica como adjuvante terapêutico.
Paracoccidioidomycosis (PCM) is a human systemic granulomatous disease, prevalent in South America, caused by a thermodimorphic fungus, Paracoccidioides brasiliensis. This fungus presents complex antigenic structure and some of these components have been related with its pathogenicity, of which little is known. The virulence recovery of isolates by passage in vivo was performed in our laboratory. Attenuated and virulent Pb18 isolates were analyzed from various angles to confirm this change. The results of the survival curve, the number of CFUs and histology, showed clear differences in pathogenicity pattern of these isolates. Other features were also evaluated as morphology, growth curve and cell ultrastructure. Analysis of differential gene expression profile showed positive regulation genes related to metabolisms of proteins, lipids and amino acids. Some molecules, previously described as putative virulence factors, were positive regulated, among which calmodulin, kex-like protein and Hsp70. However, the number of defined virulence factors for dimorphic fungal pathogens, up to now, is relatively small. Several techniques have unsuccessfully been employed to characterize these elusive antigenic structures. Using phage display methodology, three peptide-displaying phages that bound preferentially to virulent isolates of P. brasiliensis were selected. By binding assay, p04 phage distinguished predefined degrees of virulence of isolates. Using confocal microscopy, the homologue synthetic peptide (pep04), labeled with 6-FAM, was internalized by only virulent isolate yeast cells. Sequential optical section imaging indicated that the labeling was within the intracellular milieu and frequently close or overlapping DAPI staining. These results showed that both, phage p04 and pep04, can be considered as biomarkers of virulence in PCM since both bound to virulent P. brasiliensis. To evaluate the consequences of interactions between the biomarkers and fungal cells, in vitro and in vivo experiments were performed. The latter demonstrated that p04 phage was sufficient to prevent the implantation of the fungus in the lungs and its migration to spleen and liver. In addition, this phage reduced colony-forming units in the lungs of mice infected with P. brasiliensis as compared to controls. In vitro experiments showed that pep04 exhibited fungicidal activity only against virulent P. brasiliensis, leaving unaltered the growth of the attenuated isolate. Therefore, these biomarkers may be useful tools for prognosis in PCM and may be possibly used in the routine clinical practice as therapeutic drug adjuvants.
TEDE
BV UNIFESP: Teses e dissertações
Minter, Ralph. "Development of antibody technology to identify natural killer cell surface antigens in Xenopus laevis". Thesis, Durham University, 1999. http://etheses.dur.ac.uk/4598/.
Texto completoKwiatkowski, Eric. "Towards a novel group B meningococcal vaccine : peptide mimicry of capsular polysaccharide epitopes". Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324533.
Texto completoLi, Yan. "High-efficiency Blue Phase Liquid Crystal Displays". Doctoral diss., University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5399.
Texto completoPh.D.
Doctorate
Optics and Photonics
Optics and Photonics
Optics
Rao, Linghui. "Low Voltage Blue Phase Liquid Crystal Displays". Doctoral diss., University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5448.
Texto completoPh.D.
Doctorate
Optics and Photonics
Optics and Photonics
Optics
Abidi-Azzouz, Naïma. "Élaboration d'Intrabodies ciblant l'organisation conformationnelle du complexe de reverse transcription de VIH-1". Thesis, Montpellier 2, 2013. http://www.theses.fr/2013MON20050/document.
Texto completoThe rapid emergence of drug-resistant viruses against all approved HIV clinical drugs together with inaccessible latent virus reservoirs and side effects of currently used compounds have limited the potency of existing anti-HIV-1 therapeutics. Therefore, there is a critical need for new safer drugs, active against resistant viral strains. Reverse transcriptase (RT) plays an essential role in the replication of human immunodeficiency virus type 1 (HIV-1) and remains a primary target of anti-HIV-1 drugs. To develop specific HIV inhibitors, we have elaborated a new strategy based on short antibody fragments derived from the unique Heavy-chain antibodies present in Camelidae called Nanobodies that targets RT-activation. The immunization of dromedaries with RT has lead to the isolation of a panel of Nanobodies that tightly bind the two subunits of RT and inhibit its DNA-dependent DNA polymerase activity at nanomolar range. From that screen we have elaborated an intrabody (cell penetrating anti-RT Nanobody) NbRT20 that constitutes a potential interesting anti-HIV compound.We demonstrated that NbRT20 inhibits RT polymerase activity and exhibiting a potent antiviral activity with a subnanomolar IC50. NbRT20 binds the thumb subdomain and restricts its flexibility and mobility resulting in an inactive/non processive dimeric conformation of the enzyme. From a mechanistic point of view, we have showed that NbRT20 is a conformational inhibitor. it prevents proper binding of primer/template and of dNTP and destabilizes the enzyme in an inactive/non processive dimeric conformation.Taken together, these results demonstrated that, the Nanobody platform may be highly effective at generating extremely potent and selective intrabody to neutralize RT and HIV proliferation.Key words: HIV-1, RT, Nanobodies, cell penetrating peptide
Gadzekpo, Isaac Kwabena. "Selection of Phage Displaying Peptides Specific for Staphylococcus Aureus". Youngstown State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1619516455248529.
Texto completoGlökler, Jörn Felix. "Identifikation und Charakterisierung von Metallchelat-bindenden Peptiden mittels Phage-Display". [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=958911894.
Texto completoZwick, Michael Bruce. "Applications and characterization of peptides derived from phage-display libraries". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0028/NQ51943.pdf.
Texto completoStarzomski, Mark Stephen. "Characterization and applications of the phase-modulating liquid crystal display". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0016/MQ48289.pdf.
Texto completoWeber, Patric. "Display of trypanosomal antigens on the surface of filamentous phage /". [S.l.] : [s.n.], 1994. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
Texto completoDraghici, Alex-Bogdan. "Sind Antikörper gegen fusionsrelevante HIV-Fragmente mittels Phage Display generierbar?" Göttingen Sierke, 2008. http://d-nb.info/992286891/04.
Texto completoSang, Sheila J. "The Use of Phage Display to Identify Specific Peptide Ligands". Youngstown State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1409923241.
Texto completoJoulie, Michaël. "Recherche de nouvelles protéines humaines se liant à l'ADN méthylé". Thesis, Paris 11, 2011. http://www.theses.fr/2011PA112157/document.
Texto completoEpigenetic phenomena are key contributors to the function of eukaryotic genomes. These processes act on chromatin, and they are used to render the genome dynamic, but also stable throughout successive rounds of cell division. Among epigenetic processes, DNA methylation is especially well known for its role in the regulation of gene expression.In mammals, DNA methylation is strongly correlated with transcriptional repression, and fulfills at least three essential roles. First, it maintains repeated sequences transcriptionally silenced, thus ensuring the stability of the genome. Second, it is responsible for the proper regulation of parentally imprinted genes, which are crucial regulators of embryonic development and adult life. Finally, DNA methylation ensures that some tissue-specific genes are kept inactive in the organs in which they should be repressed. Besides these roles in the physiology of normal cells, DNA methylation has strong links to cancer. Indeed the pattern of DNA methylation on the genome is frequently altered in cancer cells, and these anomalies contribute to transformation by several mechanisms.DNA methylation does not control transcription directly, but instead acts via a set of dedicated proteins that specifically recognize methylated DNA and repress transcription by acting at the chromatin level. At present, three families of such proteins, totalling 9 members altogether, are known in humans. However, several lines of evidence suggest that the list is not exhaustive, and that other human proteins that bind methylated DNA remain to be found. This was the goal of the current project.To this end, we opted for two distinct types approaches, an approach based on literature and a genetic approach. The study of candidate proteins does not allow us to identify new methylated DNA binding proteins and the genetic approach by phage display revealed two proteins of interest, HMGB1 and CHD3 that must now be validated by in vivo and in vitro approaches.Furthermore, we studied the regulation of DNA repeats by Zbtb4 in mice. Preliminary results show a regulation of minor satellites by Zbtb4. The role of this regulation will be analyse further in the future
Even, Klervi. "Développement d' outils innovants pour le diagnostic et la découverte de cibles dans le cancer du sein". Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4019/document.
Texto completoIn a lifetime, 1 in 9 women will develop breast cancer, 1 of 27 will be swept away by the disease and from 10 to 15% of patients will develop metastases within three years of diagnosis. Accurate and personalized diagnosis of breast cancer and the detection of its metastatic potential is a major challenge. It is essential to develop new analytical methods allowing an effective monitoring of breast cancer. A closer analysis of the molecular characteristics of a primary tumor should lead to more effective personalized medicine, treatment and monitoring. The efficient detection of serum biomarkers would be a way to diagnose metastatic cancer and to modify treatment based on these results. Toward this goal, the proteomic analysis of patient samples has great potential but suffers from technical limitations, including the lack of a wide variety of antibodies and tumor marker. By the use of innovative antibody fragments with remarkable properties named single domain antibody (sdAb), and through the development of a new innovative strategy of phage display, this work provides important answers in terms of availability of antibody, specific proteomic analysis of sample and new target discovery. We have developed a strategy allowing the simultaneous discovery of new biomarkers and the isolation of corresponding antibodies. After the construction of sdAb libraries from llamas immunized with biopsies, and using a new in vitro selection strategy by phage display named masked selection, we have isolated breast cancer-specific antibodies
Ferreira, Fabiana Lauretti. "Identificação e avaliação de novas adesinas em Leptospira interrogans por shotgun phage display". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-15122015-091903/.
Texto completoLeptospirosis is an emerging infectious disease whose etiologic agents are pathogenic species of the genus Leptospira. Pathogenic leptospires have countless specific genes encoding proteins with unknown functions, suggesting that leptospires have unique virulence factors. Bacterial adhesins are important virulence factors and so the identification of conserved adhesins in pathogenic Leptospira species from shotgun phage display libraries, followed by selection (biopanning) in cells and/or extracellular matrix components, can reveal new antigens and strategies for leptospirosis treatment and prevention. Libraries were constructed using fragmented genomic DNA from L. interrogans and pG8SAET phagemid vector. Cloning approaches included blunt-end ligation and techniques based in cohesive-end ligation, such as ORESTES strategy and hairpin linkers. Despite some limitations, cloning by blunt-end ligation was the most efficient for library construction, being adopted for the construction of three libraries on a larger scale. Selection of new possible adhesins was performed by biopanning of the libraries in eukaryotic cells through BRASIL methodology. The first library called BBT1 exhibited approximately 106 total clones, and its biopanning resulted in four proteins fused to phage protein VIII, but none of them were expected to be exposed by the bacteria. Other libraries were built (BBT2 and BBT3) which reached the expected number of clones to obtain a larger genome representation (> 2x107 clones). Since it showed the highest proportion of positive clones, BBT2 was selected to perform a second biopanning, resulting in eleven proteins fused to phage protein VIII and/or signal peptide. In silico analysis revealed three hypothetical proteins, named LepA962, LepA069 and LepA388, that would be exposed or secreted by the bacteria, suggesting a possible adhesin function. The study of LepA388 protein led to the recognition of twelve other similar proteins belonging to a paralogous family that contains a domain called DUF_61, domain of unknown function that is present in proteins shared only among the most virulent pathogenic species of Leptospira. For this reason, the LepA388 protein was the most studied. The cloning of three portions of the protein (LepA388P, LepA388NR and LepA388F) for heterologous expression resulted in insoluble recombinant proteins, and given the presence of many cysteine residues in its structure, it was not possible to renature them appropriately. In face of the imposed obstacles, only the portion containing the sequence presented by the bacteriophage (LepA388P) was used to obtain antisera in mice, which showed high titers, demonstrating the high immunogenicity of the protein LepA388P. Recognition of native DUF_61 paralogous family proteins in extracts from distinct Leptospira serovars was not observed, as well as its in vitro expression from bacteria cultured in different conditions. Additional studies on the in vivo expression and functions of members of this family are needed for a broader understanding of their role in leptospiral biology and possibly in the pathogenesis of leptospirosis.
Revilliod, Claude. "Photo-thermochimie : mécanisme et cinétique d'une réaction de méthanation en phase gaz-solide /". [S.l.] : [s.n.], 1991. http://library.epfl.ch/theses/?display=detail&nr=956.
Texto completoStoiber, Johannes. "Hysteresis effects during martensitic phase transformations in Cu-Zn-Al shape memory alloys /". [S.l.] : [s.n.], 1993. http://library.epfl.ch/theses/?display=detail&nr=1115.
Texto completoHald, Rikke. "Generation and characterisation of a naive human antibody phage display library : a resource for clinically relevant reagents /". Cph. : Department of Pharmacology, The Danish University of Pharmaceutical Sciences, 2004. http://www.dfh.dk/phd/defences/rikkehald.htm.
Texto completoMoutel, Sandrine. "Sélection et amélioration d'anticorps recombinants, applications à la recherche fondamentale et à l'immunothérapie". Paris 6, 2009. http://www.theses.fr/2009PA066520.
Texto completoCoulon, Stéphane. "Amélioration de la Spécificité et de l'Affinité de Fragments d'Anticorps Anti-stéroïde par Mutagenèse et Phage-display". Paris 7, 2001. http://www.theses.fr/2001PA077130.
Texto completoCastel, Guillaume. "Recherche de peptides à activités antivirales ciblant le complexe de réplication/transcription des Mononegavirales". Paris 6, 2009. http://www.theses.fr/2009PA066021.
Texto completoChahboun, Siham. "Comparaison des régions variables des anticorps de macaques (Macaca fascicularis) et de l' Homme et leurs utilisation pour la neutralisation des toxines botuliques A et B". Thesis, Grenoble, 2013. http://www.theses.fr/2013GRENV022.
Texto completoOur laboratory has developed a strategy to isolate recombinant antibody fragments technology from immunized non human primates (Macaca fascicularis) by phage display. In the course of the present thesis, a comparison between macaque (Macaca mulatta) and human antibody sequences has demonstrated that antibodies of the two species are different. This difference makes the humanization of macaque antibodies desirable. The strategy was used in the framework of the European AntiBotABE project, and the screening was adapted to isolate antibody fragments cross neutralizing the B1 and B2 subtypes of botulinum B neurotoxin, by using sequentially the holotoxin BoNT/B1 and a recombinant fragment representing the C-terminal region of the heavy chain of BoNTB2. The best scFv targeting the C-terminal region of BoNT/B1 and BoNTB2 heavy chains, B2-7, demonstrated a high capacity to neutralize BoNT/B1 and BoNT/B2 in the ex vivo hemidiaphragmatic assay. A high identity (80%) between the framework regions of B2-7 and their human homologs was observed. ScFvs neutralizing BoNT/A1 by targeting its light chain were also isolated and among them, the scFv 2H8 induced a decrease of 50% in the endopeptidase activity at a concentration corresponding to a molar ratio of 2H8/BoNT/A1 of 64000. A high identity (88%) between the framework regions of 2H8 and their human homologs was also observed. Our strategy can be used to isolate other therapeutic antibody fragments