Дисертації з теми "Α/β Peptide"
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Das, Chittaranjan. "Designed β-Hairpin, β-Sheet And Mixed α-β Structures In Synthetic Peptides". Thesis, Indian Institute of Science, 2000. http://hdl.handle.net/2005/263.
Повний текст джерелаKil, Hyun Joo. "Design & Synthesis of Peptidomimetics Adopting Secondary Structures for Inhibition of p53/MDM2 Protein-protein Interaction and Multiple Myeloma Cell Adhesion." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5051.
Повний текст джерелаLopez-Perez, Elvira. "La voie α-sécrétase de maturation de la protéine précurseur du peptide β-amyloi͏̈de dans la maladie d'Alzheimer : activités protéolytiques et régulation". Nice, 2000. http://www.theses.fr/2000NICE5459.
Повний текст джерелаSaraiva, rosa Nathalie. "Synthèse diastéréosélective de molécules azotées α-trifluorométhylées - Élaboration et études conformationnelles de petits peptides incorporant des acides β-aminés trifluorométhylés". Thesis, Reims, 2017. http://www.theses.fr/2017REIMS013.
Повний текст джерелаChiral N-tert-butansulfinamides, developped by Ellman 20 years ago, have been increasingly applied for the preparation of chiral functionnalized amines, because of the affordability of both enantiomers and of their mild conditions of cleavage. However, the use of theses auxiliaries for the synthesis of quaternary trifluoromethyl derivatives remains quite limited, the corresponding trifluoromethyl ketoimines being highly unstable.Chiral N-tert-butanesulfinyl alkyl(aryl) trifluoromethyl hemiaminal ethers have been developped to be used as bench-stable surrogates of these ketoimines : once under reaction conditions, they afford the corresponding ketoimine in situ, which can be subject to a nucleophilic addition.In this manuscript, different reactions led on these hemiaminal ethers are described, affording valuable and optically pure trifluoromethylated quaternary building-blocks : on the one hand, homoallylic amines, obtained by the addition of allylalane species, and which can afford, after a few steps, teh corresponding trifluoromethyl azetidines, and on the other hand, chiral trifluoromethyl β3,3-amino acids, afforded by a highly diastereoselective Reformatsky reaction.These β 3,3-amino acids have been then involved in solution-phase peptide couplings in order to synthetise a wide range of α/β- and β-di- and tripeptides, whose conformation have been the object of preliminary studies in the solid state and/or in solution.Key-words : Ellman auxiliary, Nucleophilic addition, Solution-phase peptide coupling, α-trifluoromethylated nitrogen derivative, Hemiaminal ether, asymmetric synthesis
Attal, Sandra. "Utilisation des enzymes en chimie organique : application à la synthèse d'esters de dipeptides par la papai͏̈ne et de galactosyl-sérines par les α-et β-galactosidases". Paris 5, 1992. http://www.theses.fr/1992PA05P614.
Повний текст джерелаCollet, Magalie. "Peptidonucléoside polyoxine J, inhibiteur de la chitine synthase : approches vers la synthèse du nucléoside C2' - désoxy -C2' fluoré, et synthèse de l'acide 5-O-carbamoyle polyoxamique." Toulouse 3, 2004. http://www.theses.fr/2004TOU30198.
Повний текст джерелаPolyoxins, which form an important class of peptidyl nucleosidic antibiotics that selectively and competitively inhibit chitin synthase, are very active components in vitro, but weakly bioavailable in vivo. The subject of this thesis has been to found new synthetic methods to access to C2'-fluoro-C2'-deoxy analogues of thymine polyoxine C, nucleosidic part of polyoxine J (the more active one), and to obtain, by an original way, the non natural peptidic moiety of polyoxine J, which is the 5-O-carbamoyl polyoxamic acid. After a presentation of the biological target and the interest of the introduction of a fluorine atom, this work is divided into two parts. Fisrt, two approaches of the fluorinated nucleosodic part using 2-deoxy-2-fluorobutyrolactones as intermediates, and then, an optimization of the synthesis of the peptidic part using the formation of an oxazolidonone intermediate
Norgren, Anna S. "Conformational Stability!? : Synthesis and Conformational Studies of Unnatural Backbone Modified Peptides." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7420.
Повний текст джерелаPatino, Nadia. "Peptides fluorés : intérêt et synthèse de peptides incorporant dans leur structure un acide α-aminé β-fluoré". Nice, 1989. http://www.theses.fr/1989NICE4274.
Повний текст джерелаWillems, Hendrika Maria Gerarda. "The design and synthesis of non-peptidic α-helix and β-turn mimetics". Thesis, University of Cambridge, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627463.
Повний текст джерелаClaudel, Stéphanie. "Les peptides Vinylogues : des nouveaux outils pour la préparation d'analogues contraints de la substance P, de γ-aminoacides α, β-hydroxylés et de dihydroxylactames". Nancy 1, 2004. http://www.theses.fr/2004NAN10039.
Повний текст джерелаThis work concerns conception and synthesis of modified peptides and is divided in two parts. Firstly, it's the insertion of vinylogous amino acids with cis and trans conformation in neuropeptide of eleven amino acids which is substance P in order to understand its interaction with NK-1 receptor. A second study has been oriented on the preparation of g-amino peptides by hydrogenation of previous vinylogous amino acids. This structural modification has given a new SP's analog which has been tested. The second part is the methodology of synthesis using vinylogous peptides and is divided in three chapters. First one presents dihydroxylation's results of these residues with an asymmetric induction using chiral catalyst to obtain dihydroxylated g-amino acids. Second one is an application of these studies with a total synthesis of natural product extracted from nyctinastic plant. And the last one deals with preparation of dihydroxylated lactams leading to the synthesis of new azasugars
Jégou, Sylvie. "Etude des peptides apparentés à la proopiomélanocortine dans le système nerveux central." Rouen, 1990. http://www.theses.fr/1990ROUE5012.
Повний текст джерелаThornley, Thomas B. "IFN-α/β Induction by dsRNA and Toll-Like Receptors Shortens Allograft Survival Induced by Costimulation Blockade: A Dissertation". eScholarship@UMMS, 2006. https://escholarship.umassmed.edu/gsbs_diss/254.
Повний текст джерелаEzpeleta, Juliette. "Du rôle physiologique de la protéine prion cellulaire à l'infection par les prions : régulation/dérégulation du module de signalisation PDK1/TACE α-secrétase Protective role of cellular prion protein against TNFα-mediated inflammation trough TACE α-secretase Cerebellar compartmentation of prion pathogenesis Production of seedable Amyloid-β peptides in prion diseases upon PrPSc-induced PDK1 overactivation". Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCB004.
Повний текст джерелаPrion diseases are neurodegenerative disorders characterized by the accumulation into the central nervous system of an abnormally folded protein called Scrapie prion protein (PrPSc). PrPSc is the transconformational isoform of a ubiquitous protein of the host named cellular prion protein (PrPC). It is well established that the toxicity of PrPSc is restricted to neurons and arise from a corruption of the physiological function(s) of PrPC. However, the mechanisms by which PrPSc exerts its neurotoxicity remain poorly understood, partly because the physiological function(s) of PrPC is/are still elusive. Currently, no one knows if PrPC loses a protective role or acquires a toxic function upon its conversion into PrPSc, a combination of both events is also possible. Identifying PrPC-associated function(s) is thus a prerequisite to understand how PrPSc provokes neurodegeneration. The present work reports for the first time a protective role of PrPC towards the pro-inflammatory cytokine sTNF-alpha-associated toxicity. We show that PrPC adjusts cell sensitivity to sTNF-alpha by controlling TACE-dependent TNFR1 shedding. Mecanistically, PrPC governs both (i) TACE activity, through PrPC coupling to NADPH oxidase/Reactive Oxygen Species production, and (ii) TACE localization, by downregulating the beta-1 integrins/ROCK/PDK1 signaling pathway, thus PrPC ensures the bioavailability of an active TACE at the plasma membrane. PrPC depletion provokes the micro-aggregation of beta-1 integrins, the overactivation of ROCK and PDK1 kinases, and the subsequent internalization of TACE into Caveolin-1 enriched micro-vesicles. This leads to a defect of TNFR1 shedding, which accumulates at the plasma membrane and renders PrPC-depleted neurons highly vulnerable to sTNF-alpha insult. These alterations have also been reported in prion-infected neurons with the same intensities, supporting the view that a loss-of-the protective function of PrPC towards sTNF-alpha likely occur along prion diseases. Within a prion infectious context, a collaborative work revealed that the cerebellar Purkinje cells that do not express zebrins are highly vulnerable to the toxicity of two prion strains, 22L and ME7, compared to Purkinje cells that express zebrins. This suggest a protective role of zebrins against PrPSc-associated toxicity. A major part of my thesis identifies a new target deregulated downstream from the PDK1/TACE signaling module, the amyloid precursor protein (APP), well-known for its implication in Alzheimer's disease. By abrogating the non-amyloidogenic cleavage of APP by TACE, PrPSc provokes the overproduction of Abeta40/42 peptides. Abeta40/42 predominates as monomers but are also found as multimeric assemblies, i.e. trimers and tetramers. PrPSc-induced Abeta40/42 overproduction relates to PDK1 overactivation as pharmacological inhibition of PDK1 attenuates production of Abeta monomers and renders multimers undetectable. Of note, our work reveals that Abeta peptides do not impact on PrPSc replication nor infectivity. Nevertheless, Abeta40/42 peptides generated upon prion infection can deposit in mice brains only if an exogenous Abeta seed is co-transmitted with PrPSc. Importantly, Abeta deposition leads to early death of prion-infected mice. This work delineates the conditions that allow Abeta plaques formation and highlights the onset of a mixed-pathology caused by the co-occurrence of PrPSc and Abeta deposition within a prion infectious context
Boudet-Devaud, François. "La protéine prion cellulaire : un relai de neurotoxicité commun aux protéines amyloïdes et aux nanoparticules Protective role of cellular prion protein against TNFα-mediated inlammation through TACE α-secretase PrPSc-induced PDK1 overactivation promotes the production of seedable Amyloid-β peptides in prion diseases Corruption of cellular prion protein signaling by titanium dioxide or carbon black nanoparticles promotes the accumulation of amyloid-β peptides". Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB127.
Повний текст джерелаThe cellular prion protein (PrPC) is a protein mostly expressed at the plasma membrane of neurons. Its transconformation into the pathogenic prion PrPSc is at the root of prion diseases. It is clearly established that the PrPSc-induced neurodegeneration depends on the expression of PrPC in neurons and results from the corruption of PrPC function(s) by PrPSc. Unravelling the role of PrPC is thus a prerequisite to grasp neurodegeneration mechanisms in prion diseases. Part of my work shows that PrPC exerts a cytoprotective function against TNFalpha inflammatory cytokine. PrPC silencing in neurons (PrPnull-neurons) renders these cells highly sensitive to TNFalpha due to surface accumulation of TNFalpha receptor (TNFR). My work demonstrates that the loss of PrPC regulatory function on the clustering and signaling downstream of bêta 1 integrins in PrPnull neurons provokes the overactivation of the kinase PDK1, subsequent internalization of TACE alpha-secretase, and uncoupling of TACE from TNFR substrate. Because of the phenotypic proximity between PrPnull neurons (Ezpeleta et al. 2017) and PrPSc-infected neurons (Pietri et al. 2013; Alleaume-Butaux et al. 2015), my work supports the view of a loss of PrPC protective function in prion diseases. As concerns prion infection, my work shows that after PDK1 overactivation, internalized TACE is uncoupled from another substrate, the amyloid peptides precursor protein (APP), leading to the accumulation of neurotoxic peptides Abêta 40 and Abêta 42, hallmarks of Alzheimer's disease. Within a prion infectious context, Abêta 40/42 peptides are predominantly present as monomers, and to a lesser extent, as trimers and tetramers. By combining in vitro and in vivo approaches, we show that Abêta peptides produced by infected neurons do not alter replication nor the infectivity of prions. Nevertheless, we demonstrate that oligomerized Abêta is able to form amyloid plaques in the brain of transgenic APP23 mice infected by prions. In these mice, Abêta deposits accelerate prion pathogenesis. The last axis of my work deals with nanoparticles, that is, nanometric materials commonly found in manufactured products and industrial processes. My work shows that, as PrPSc and Abêta, titanium dioxide or carbon black assemblies interact with PrPC at the surface of neurons and deviate its signaling function, which leads, inter alia, to PDK1 overactivation, TACE internalization, TNFR accumulation at the plasma membrane, and neuronal cells hypersensitivity to TNFalpha inflammatory stress. We also found that nanoparticle-induced TACE uncoupling from APP increases Abêta peptide production by neurons. Even if no epidemiological study has demonstrated to date a link between nanoparticle exposure and Alzheimer's disease, my work suggests an causal implication of nanoparticles in the initiation or amplification of this disease
Vasudev, Prema G. "X-Ray Crystallographic Studies Of Designed Peptides : Characterization Of Novel Secondary Structures Of Peptides Containing Conformationally Constrained α-, β- And γ-Amino Acids And Polymorphic Peptide Helices". Thesis, 2009. http://hdl.handle.net/2005/922.
Повний текст джерелаSonti, Rajesh. "Conformational Analysis of Designed and Natural Peptides : Studies of Aromatic/Aromatic and Aromatic/Proline Interactions by NMR." Thesis, 2013. http://etd.iisc.ernet.in/2005/3335.
Повний текст джерелаRoy, Rituparna Sinha. "Conformational Analysis Of Designed Alpha-Omega Hybrid Peptides." Thesis, 2005. http://etd.iisc.ernet.in/handle/2005/1500.
Повний текст джерелаLagace, Melissa. "Effect of α-lactalbumin and β-lactoglobulin hydrolysates on markers of metabolic syndrome". 2012. http://hdl.handle.net/1993/8617.
Повний текст джерелаLinㄝRen-Jie та 林仁傑. "Theoretical Investigation of Site Specificity on OH α-H Abstraction Reaction Using a Zwitterionic β-hairpin Peptide as an Example". Thesis, 2013. http://ndltd.ncl.edu.tw/handle/aya7w8.
Повний текст джерела國立中興大學
化學系所
101
Protein backbone oxidation was investigated by studying the α-H abstraction reaction in a s-hairpin peptide, called Chignolin (PDB ID 1UAO), with density functional theory calculation at B3LYP/6-31G(d,p) without any constraint. In order to stabilize the zwitterionic form of Chignolin with the salt bridges, the effects of aqueous solution were implemented by using microsolvation combined with a conductor-like polarizable continuum model (CPCM). Comparison between three glycine residues located at three different sites in Chignolin was used to examine the possible site specificity of this backbone oxidation. To construct the reaction profile of these α-H abstraction reactions, the pre- and post-reactive complexes along with their associated transition states were located and verified with the intrinsic reaction coordinate (IRC) method. The bond dissociation energy and reaction rates of these OH α-H abstraction reactions were calculated with transition state theory. The differences in this abstraction reaction between the neutral and zwitterionic forms of Chignolin were also compared. A molecular dynamics simulation was implemented to study the explicit solvation effect on the abstracted Chignolin structure. The range of the simulation time scale covers from fs to ns, i.e., from onset of the abstraction to the abstracted products reaching thermal equilibrium. Our results show that there are three kinds of site-specificity in this abstraction reaction. The reactivity and stability of the abstraction products and their abstraction modes are all dependent on the location where OH attacks. Furthermore the free energy landscapes of these abstraction products are distinctively different. This may imply the pathological disorders or diseases caused by this type of radicals are also dependent on the abstraction location.
Lin, Lee Sheng, та 林立盛. "Synthesis of 2,6-dimethoxyhydroquinone-3-mercaptoacetyl conjugates of TNF-α-(30-35) and TNF-β-(106-110) and di- peptide derivatives as potential antitumor agents". Thesis, 1995. http://ndltd.ncl.edu.tw/handle/67632338519046261859.
Повний текст джерелаGeranurimi, Azade. "Lactam-peptide modulators of biased interlukin-1 receptor signaling for mitigating inflammation without compromising immuno-vigilance." Thesis, 2019. http://hdl.handle.net/1866/23926.
Повний текст джерелаPreterm birth (PTB) is an unmet biomedical need. Despite efforts to counter the onset of preterm labor, the rate of premature birth has increased steadily in developed countries. The interleukin-1 receptor (IL-1R) has been pursued as a target for designing agents which can prolong labor and improve neonatal outcomes. Towards these goals, a lead peptide 101.10 had been shown to modulate the IL-1R, to delay PTB and to mitigate associated retinopathy of prematurity (ROP) by an allosteric mechanism featuring biased signaling. With the goals of understanding the active conformers and improving the activity of 101.10, methods were conceived for the synthesis and introduction of β-substituted α-amino γ-lactams into peptides. Applying such methods on 101.10 has provided insight into the structure-activity relationships required for allosteric modulation of the IL-1R. Peptidomimetics are promising structures that replicate peptide function and conformation. They offer the potential to improve molecular-recognition, to enhance transport across biological membranes, and to resist metabolism. Among peptidomimetic classes, α-amino γ-lactam (Agl) residues introduce covalent constraint to rigidify the peptide backbone and have been employed to favor turn secondary structures. β-Substituted Agl analogs offer additional potential to mimic and restrict peptide side-chain geometry. This thesis introduces effective methods for the stereo-controlled synthesis of β-substituted α-amino γ-lactams residues having various side chain functionality. Introduction of the parent Agl residue and β-substituted counterparts into biologically active peptides has been explored to study structure-activity relationships. Employing the IL-1R modulator 101.10 as a representative peptide, the described research has furnished novel labor delaying agents that can improve neonatal outcomes. In chapter 2, α-amino-γ-lactam (Agl) and β-hydroxy-α-amino-γ-lactam (Hgl) stereoisomers were employed to study the influence of configuration and hydroxyl group side chain on conformation and activity of the interleukin-1 receptor modulator peptide 101.10. The configuration and hydroxyl group side chain influenced the conformation and biological activity of Agl and Hgl-101.10 analogs. Circular dichroism (CD) spectroscopy illustrated β-turn conformers for specific analogs, such as [(3R,4S)-Hgl3]-101.10. The Agl and Hgl analogs were examined in a series of in vitro assays and in vivo models of PTB. Contingent on their structure vi and configuration, the lactam analogs exhibited different functional selectivity in the various biological pathways, and indicated the requirement for specific phenotypes. For example, inhibition of the JNK and ROCK kinase pathways were respectively shown to be important for delaying labor and diminishing vaso-obliteration in the PTB and ROP models. Notably, among the twelve analogs, [(3R,4S)-Hgl3]-101.10 was found to exhibit identical in vitro and in vivo activity as the parent peptide. In chapter 3, methods were developed for displacement of the β-hydroxy-α-amino-γ-lactam (Hgl) residue alcohol to introduce stereo-selectively different β-substituents on Agl residues. A combination of Mitsunobu chemistry on the trans Hgl residue, and nucleophilic ring opening of the cyclic sulfamidate derived from the cis lactam counterpart provided constrained mimics of Ser, Thr, Cys, Dap, Dab, His and Met residues. In chapter 4, various β-substituted lactams were introduced into the sequence of 101.10 by combination of solution and solid phases chemistry to further study the structural requirements for regulating the activity and signaling of this key cytokine mediator of inflammasome activation. Considering the activity of [(3R,4S)-Hgl3]-101.10, the β-substituted Agl analogs were synthesized possessing similar backbone and side chain configurations. Certain analogs exhibited promising biological activity in the ROP model meriting further study. In sum, methods were conceived for the synthesis and application of α-amino-γ-lactams and their β-substituted analogs to study peptide structure-activity relationships. Employing this chemistry on the IL-1R allosteric modulator 101.10 has identified the active conformer and in vitro activity responsible for ability to delay labor and mitigate retinopathy of prematurity. Considering the utility of the lactam synthesis methods for the development of improved agents for delaying labor and improving neonatal outcomes, this thesis has conceived useful prototypes for drugs to treat PTB, as well as useful methods for dissecting the structural requirements for peptide chemical biology.
Rudresh, *. "De Novo Design Of Protein Secondary And Super Secondary Structural Elements: Investigation Of Interaction Patterns From The Crystal Structure Analysis Of Oligopeptides Containing α,β-Dehydrophenylalanine Crystal Structure Analysis Of Double Mutant M37L, P40S Thioredoxin From E.Coli". Thesis, 2006. http://hdl.handle.net/2005/331.
Повний текст джерелаZorn, Chiara [Verfasser]. "Synthesis and structural investigations of α-peptides [alpha-peptides] containing β-aminocyclopropane [beta-aminocyclopropane] dicarboxylic acids / vorgelegt von Chiara Zorn". 2002. http://d-nb.info/965506843/34.
Повний текст джерелаTsai, Hsin-Yun, та 蔡幸芸. "Effect of Side Chain Length on Ion Pairing Interaction in β-Hairpins and Diverse α/β-Mixed Backbone Peptides for Calmodulin Inhibition". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/39475782566290235089.
Повний текст джерела國立臺灣大學
化學研究所
101
β-Sheet is a common secondary structure. The structure can be stabilized by cross strand interactions such as backbone hydrogen bonds and side chain electrostatic interactions. Ion pairing interactions can form between two oppositely charged amino acids, such as Lys, Arg, Glu, and Asp. However, some unnatural amino acids contain different number of methylene groups in the side chain are not incorporated in natural proteins. Accordingly, the ion pairing interaction involving Asp-Lys, Asp-Orn, and AspDab were investigated in a β-hairpin system. The 2D-NMR spectra including TOCSY, ROESY, and COSY were acquired for the peptides. The peptide β-hairpin structure as confirmed by chemical shift deviations, 3JNHα coupling constants, and NOE connectivities. The β-hairpin population and stability were determined by comparing the chemical shifts with the reference peptides. The peptide stability followed the trend HPTAspLys ~ HPTAspOrn > HPTAspDab. The ion pairing interactions were derived from double mutant cycles. The corresponding ion pairing interactions followed the trend Asp-Lys ~ Asp-Orn ~ Asp-Dab. Calmodulin (CaM) is a highly conserved and abundant protein in eukaryotic cells. Calmodulin participates in many physiological processes, such as muscle contraction, insulin and pituitary secretion, and neurotransmission. CaM can bind to basic amphiphilic α-helical peptides. To control the 3D-arrangement of side chains and minimize proteolytic degradation, β-amino acids were incorporated into peptides. β-Amino acids are unnatural amino acids containing one extra methylene group in the backbone compared to natural α-amino acids. In this study, the side chain sequences of peptides were the same as the basic amphiphilic α-helical peptide, but the backbone patterns were varied by mixing α- and β-amino acids, including αβ, ααβ, αααβ, and ααβαααβ. The binding affinities were determined by CD spectroscopy and fluorescence anisotropy. The proteolytic susceptibilities were tested against trypsin.
De, Pol Silvia [Verfasser]. "Synthesis, conformational investigations and applications of α-peptides [alpha-peptides] containing cis-β-aminocyclopropane [cis-beta-aminocyclopropane] dicarboxylic acids / vorgelegt von Silvia De Pol". 2007. http://d-nb.info/983860238/34.
Повний текст джерелаKosten, Marc [Verfasser]. "Beitrag zur Chemie der 2, 3, 4, 5-Tetrahydropyridine : Synthese von cyclischen β-Aminosäuren, β-Lactamen und β-Peptiden sowie schwefelhaltigen γ- und δ-Lactamen und α-Aminophosphonsäurederivaten / von Marc Kosten". 2003. http://d-nb.info/967061075/34.
Повний текст джерелаNataraj, D. V. "Studies on Turns in Proteins - Data Analysis and Conformational Studies on α -Turns". Thesis, 1996. http://hdl.handle.net/2005/3218.
Повний текст джерелаBagaria, Ashima. "Crystal Structure Of Abrus Precatorius Agglutinin-I (APA-I) : Insights Into The Reduced Toxicity Of APA-I In Relation To Abrin. Formation Of Ordered Nanotubes Through Self Assembly In The Crystal Structures Of Dipeptides Containing α. β-dehydrophenylalanine". Thesis, 2007. http://hdl.handle.net/2005/567.
Повний текст джерела