Дисертації з теми "Γ-peptides"
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Qureshi, Muhammad Khurram Naseem. "Foldamers based on γ-peptides". Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611289.
Повний текст джерелаStanovych, Andrii. "Synthèse et études structurales de γ-peptides synthétisés à partir d’acides β,γ-diaminés". Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112310/document.
Повний текст джерелаThe design of a new oligopeptides, capable to mimic the properties of natural proteins, is an important field not only for structural studies but also in the developpement of new efficient drugs. The peptides featuring β-amino acids have been extensively explored, whereas the research in γ-peptides is more recent. The studies of γ-peptides show their ability to adopt stable secondary structures and also to have a promising biological activity. Our laboratory is interested in the synthesis of new β,γ-diaminoacids.The aim of this work is a developpement of new synthetic route starting from different natural α -amino acids and to use obtained β,γ-diaminoacids to access novel unnatural peptides having specific conformational properties.The synthetic strategy, developed and optimized in our laboratory during this work, gives access to diastereomers cis and trans from L-leucine, L- and D-phenylalanine which were used in the synthesis of a new hybrid α/γ-peptides. The structural studies were performed on two series of hybrid α/γ-peptides consisting of β,γ-aminoacid from L-leucine and L- or D-α-amino acids. In the first case, the peptides are able to adopt stable secondary structures stabilized by intramolecular hydrogen bonds involving the nitrogen on the β-position. In addition, we present the synthesis of an analogue of gramicidine S, a naturally occuring antibiotic cyclic peptide. The dipeptide pattern D-Phe-L-Pro has been replaced with the β,γ-diaminoacid synthesized from D-phenylalanine
Bouillère, Francelin. "Synthèse stéréosélective d'acides β,γ-diaminés : applications à l'étude structurale de nouveaux peptides". Paris 11, 2010. http://www.theses.fr/2010PA112359.
Повний текст джерелаInterest in unnatural oligomers with strong conformational propensities (« foldamers ») akin to those of proteins has led to numerous recent explorations in this field. These oligomers are interesting targets as they can be valuable for specific applications such as protein-protein interactions or antibodies activity. The aim of this work is both to allow the development of a new synthetic route to enantiopure β,γ-diaminoacids and to use them to access to novel peptides having specific conformational properties
Migliore, Mattia. "Recherche par modélisaion moléculaire de signatures RMN et DC caractéristiques pour les coudes β et y dans les peptides bioactifs. Characterization of β-turns by electronic circular dichroism spectroscopy : a coupled molecular dynamics and time-dependent density functional theory computational study". Thesis, Normandie, 2020. http://www.theses.fr/2020NORMR001.
Повний текст джерелаThe aim of this work is to identify NMR and CD characteristic patterns for β- and γ-turns in bioactive peptides by molecular modelling. With helices, β- and γ-turns constitute favoured recognition motifs in bioactive peptides by their targets. Even though several classes of turns with different geometries exist in polypeptide structures (2 γ-turn types and 12 β-turn types), few experimental tools are available for their characterization. Thus, only 4 types of β-turns (I, I’, II et II’) have been, at present, described by NMR and there are no reliable reference CD spectra for turns. In order to extend the NMR data for all β- and γ-turn types, we analyzed NMR structural parameters (inter-hydrogen distances and ᶾJʜɴ-ʜꭤ coupling constants) in a representative peptide model dataset extracted from the PDB. The inter-hydrogen distance analysis allowed to identify specific NMR patterns for the two γ-turn types and for four β-turn types (IV₁, IV₂,, VIb and VIII). ᶾJʜɴ-ʜꭤ coupling constant may be used to confirm the identification and to remove ambiguities. Then, we simulated the reference CD spectra of model peptides adopting type I, I’, II and II’ β-turn conformations by combining molecular dynamic simulations and TDDFT computations. These computations allowed to determine two families of specific CD spectra : types I/II’, on one side and types I’/II, on the other. All these results indicate that the turns do not present the same patterns in both techniques. The combination of NMR and CD could therefore allow a better identification of the nature and the different types of turns
Itkin, Anna. "Multidisniplinary study of Alzheimer's disease-related peptides : from amyloid precursor protein (APP) to amyloid β-oligomers and γ-secretase modulators". Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAF051/document.
Повний текст джерелаA histopathological characteristic of Alzheimer’s disease (AD) is the presence of amyloid plaques formed by amyloid β(A) peptides of 40 and 42 residues-long, which are the cleavage products of APP by proteases. To understand the role of structural changes in the TM domain of APP, APP_TM4K peptides were studied in the lipid bilayer using ATR-FTIR and ssNMR. While the overall secondary structure of the APP_TM4K peptide is helical, conformational and orientational heterogeneity was observed for the y- and for the -cleavage sites, which may have implications for the cleavage mechanism and therefore the production of Aβ. Starting from its monomeric form, Aβ peptides aggregate into fibrils and / or oligomers, the latter being the most neurotoxic. We found that in the presence of Ca2 +, Aβ (1-40) preferably forms oligomers, whereas in the absence of a2 + Aβ (1-40) aggregates into fibrils. In samples without Ca2 +, ATR-FTIR shows conversion from antiparallel β sheet conformation of oligomers into parallel β sheets, characteristic of fibrils. These results led us to conclude that Ca2 +stimulates the formation of oligomers of Aβ (1-40), that have been implicated in the pathogenesis of AD. Position and precise orientation of two new drugs powerful modulators of γ-secretase benzyl-carprofen and carprofen sulfonyl in the lipid bilayer were obtained from neutron scattering and ssNMR experiments. These results indicate that carprofen-derivatives can directly interact with APP. Such interaction would interfere with proper APP-dimer formation, which is necessary for the sequential cleavage by β -secretase, diminishing or greatly reducing Aβ42 production
Rosés, Subirós Cristina. "Solid-phase synthesis of cell-penetrating γ-peptide/antimicrobial peptide conjugates and of cyclic lipodepsipeptides derived from fengycins". Doctoral thesis, Universitat de Girona, 2016. http://hdl.handle.net/10803/393895.
Повний текст джерелаAquesta tesi doctoral s’ha centrat en el desenvolupament d’estratègies sintètiques útils per a l’obtenció de nous pèptids bioactius. Primerament, s’han dissenyat nous pèptids conjugats antitumorals a través de la unió d’un pèptid antimicrobià i un cell-pentrating peptide. Aquesta conjugació augmenta l’activitat antitumoral del pèptid mantenint la toxicitat baixa. Aquests conjugats són interessants pel desenvolupament de nous agents antitumorals. A continuació, s’ha desenvolupat una metodologia per a la preparació de pèptids cíclics derivats de les fengicines. Aquesta metodologia representa la primera estratègia sintètica descrita per a l’obtenció en fase sòlida d’aquesta família de ciclolipodepsipèptids i pot ser fàcilment adaptada per a l’obtenció d’una àmplia varietat d’anàlegs.
Claudel, 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
Mazzier, Daniela. "Functionalized short peptides and polypeptides: from organic reactions, through secondary structure control, to supramolecular applications." Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3424844.
Повний текст джерелаPeptidi elicoidali corti In questo lavoro di tesi sono stati studiati diversi peptidi caratterizzati da una ben definita conformazione elicoidale con lo scopo di stabilizzarne la struttura secondaria oppure di sfruttare la loro conformazione rigida come mezzo per controllare l’induzione asimmetrica su lunghe distanze. Il primo esempio, un sistema oligopeptidico biciclico doppiamente stabilizzato, è stato ottenuto tramite due reazioni di macrociclizzazione che hanno coinvolto le catene laterali dei residui in posizione i e i+4 di un peptide lineare. Un’indagine conformazionale dettagliata, condotta utilizzando le spettroscopie CD ed NMR, ha rivelato che la conformazione mista 310/α-elica, osservata per il peptide lineare, risulta completamente convertita in una struttura ad elevato contributo α-elicoidale nel peptide biciclico. In parallelo, sia il contenuto totale di elica sia la stabilità risultano significativamente aumentati. Nel secondo caso, un foldamero achirale elicoidale a base di Aib è stato opportunamente funzionalizzato con il gruppo fotoisomerizzabile fumarammide/maleammide contenente un residuo chirale. In questo modo è stato ottenuto un sistema in cui è stato possibile influenzare il senso di spiralizzazione dell’elica grazie all’uso di luce ultravioletta. La configurazione trans nella fumarammide, infatti mantiene il residuo chirale lontano dal segmento achirale dell’oligomero, rendendo impossibile l’induzione di una conformazione preferenziale. Tuttavia dopo l’isomerizzazione, la configurazione cis della maleammide consente alla parte chirale e a quella achirale di essere spazialmente vicine, con conseguente induzione di chiralità e adozione di un senso preferenziale di spiralizzazione. Sfruttando questo principio è stato quindi possibile utilizzare la luce per accendere o spegnere la capacità del sistema di reagire stereoselettivamente, oppure di modulare la comunicazione di chiralità tra due segmenti elicoidali. Polipeptidi elicoidali funzionalizzati Con lo scopo di ottenere tramite self-assembly microstrutture con differenti caratteristiche, forme e funzioni sono stati sintetizzati diversi sistemi coniugati a base di poli(γ-benzil-L-glutammato) (PBLG). Sistemi polipeptidici contenenti una o due unità di fullerene sono stati ottenuti tramite reazione tiol-ene one-pot. Questi due polimeri hanno mostrato una diversa propensione ad auto-assemblarsi in ambiente acquoso, formando microstrutture di forma toroidale oppure di tipo vescicolare. Come ulteriore esempio è stata riportata la sintesi di sistemi coniugati a base di PBLG e carbon quantum dots. I CQDs, preparati per trattamento in microonde a partire da una soluzione acquosa di arginina e 1,2-etilendiammina, sono stati usati come iniziatore, ottenendo una struttura polimerica a forma di stella, oppure come agente cappante, portando alla formazione di microstrutture più complesse. I sistemi ottenuti sono in grado di autoassemblarsi formando aggregati supramolecolari di forma sferica che mantengono le caratteristiche proprietà di emissione dei dots originali. Infine, microstrutture “smart” con comportamento fotoresponsivo sono state ottenute inserendo amminoacidi a base di azobenzene all’interno del sistema polipeptidico. Sono state quindi sintetizzate due strutture polipeptidiche con simmetria C2 e C3 che hanno evidenziato la formazione di strutture sferiche tramite self-assembly. Il cambiamento della loro struttura tridimensionale in seguito ad irraggiamento è accompagnato da una variazione nella morfologia degli aggregati. Peptidi corti auto-assemblanti In questo ultimo capitolo sono discusse la sintesi e le peculiari proprietà di self-assembly mostrate da due diversi sistemi peptidici. La prima serie di composti contiene l’amminoacido fotoisomerizzabile bis[p-(fenilazo)benzil]glicina, che è in grado di isomerizzare reversibilmente tra le due forme cis/trans in seguito ad irraggiamento con luce di adeguata lunghezza d’onda. Derivati e peptidi corti contenenti questo amminoacido sono in grado di promuovere la formazione di strutture supramolecolari ordinate. Inoltre, grazie alla presenza delle due unità di azobenzene sulle catene lineari, la transizione morfologica osservata in seguito ad irraggiamento si è dimostrata essere reversibile. Nella seconda parte di questo studio è stato esaminato il comportamento del dipeptide idrofobico protetto Boc-L-Cys(Me)-L-Leu-OMe. La formazione di nano-, micro- e macro- architetture complesse, tra cui bacchette caratterizzate da una cavità interna, è stata osservata in diverse condizioni sperimentali. I risultati ottenuti suggeriscono che le proprietà di self-assembly sono correlate all’organizzazione delle molecole nel cristallo singolo in cui è stata osservata la presenza di una particolare struttura supramolecolare elicoidale formata da sei molecole. Successivamente è stato deciso di modificare il dipeptide in modo da ottenere un derivato diacetilenico. Questo derivato è in grado di formare un organogel o delle strutture sferiche che possono subire polimerizzazione topochimica per irraggiamento UV.
Romero, Eugénie. "Synthèse et étude conformationnelle d’α-hydrazinopeptides linéaires et cycliques". Thesis, Université de Lorraine, 2015. http://www.theses.fr/2015LORR0232/document.
Повний текст джерелаThe formation of nanostructures with well-defined organic brick self-assembly has received much attention due to their potential applications in chemistry and biology. Among all these organic elements, peptides and pseudopeptides are among the most promising because of their similarity to proteins. We can enumerate many peptides self-assembly, such as nanotubes, nonafibres, vesicles, nanospheres etc … In this context, we are interested by the synthesis and overall structural study of hydrazinopeptides. Thanks to the additional nitrogen, these bis-nitrogen pseudopeptides are able to self-assemble into new structuring. The 1:1[α/α-Nα-Bn-hydrazino] linear peptides showed coalesce into hydrazinoturn and γ-turn in solution. We have highlighted the ability of analogues of 1:1[ß/α-Nα-Bn-hydrazino] linear peptides to be structured in hydrazinoturn only, in solution. Similarly, we have demonstrated the ability of pure α-Nα-Bn-hydrazino pseudopeptides to be structured in a very solid solution structure formed of hydrazinoturn observable also in crystal state. Secondly, and as part of the development of nanotube structures, we have studied a serie of 1:1[α/α-Nα-hydrazino] cyclic peptides, and especially cyclotetrameres. In this context, we have sought to highlight the various parameters that may affect the organization in nanotubes, in order to develop the best strategy to achieve this potential application in nanostructuring views. The various parameters studied are: the synthetic strategy, the chirality, the orientation of side chains, and finally the ability to form gels
Wan, Yang. "Synthesis of β,γ-diamino acids and their use to design new analogues of the antimicrobial peptide Gramicidin Septide antimicrobien, la Gramicidine S". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS407/document.
Повний текст джерелаIn our group, we are interested in developing peptides containing β,γ-diamino acids . Along with many other peptides containing unnatural amino acids, they have shown the ability to possess stable conformations and/or interesting biological activities. Moreover, those peptides are usually more resistant to proteolysis. In order to synthesize stereopure γ-amino acids, we have developed a synthetic route using Blaise reaction and subsequent diastereoselective reduction as key reactions. Through applying this method, we have synthesized β,γ-diamino acids derived from D-phenylalanine and L-glutamic acid. The former β,γ-diamino acid was used for designing antimicrobial peptide gramicidin S analogues. Compared with mother molecule, the analogues exerted much less host cell cytotoxicity while remaining interesting antibacterial activity. Meanwhile, it gave us more knowledge for further developing analogues of gramicidin S as well as other antimicrobial peptides. We also paid lots of effort to efficiently synthesize cyclic β,γ-diamino acids starting from L-glutamic acid. Interestingly, when oligomers incorporating this β,γ-diamino acids and α-amino acids, they have shown the potential to adopt stable conformations. The following studies will be continuously investigated
Georgsson, Jennie. "Design and Synthesis of Novel AT2 Receptor Ligands : From Peptides to Drug-Like Molecules." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6269.
Повний текст джерелаMesserschmitt, Alexandre. "Utilisation d’unités γ-lactames pour le développement de vecteurs de pénétration intracellulaire et la conception de foldamères". Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTS018/document.
Повний текст джерелаThe use of α-amino-γ-lactam oligomers (Agl-αAA) as cell penetrating vectors are described in this work. These ribbon structured oligomers are able to cross the cell membrane to reach the cytosol and deliver a biologically active cargo. Unlike peptide sequences, these oligomers display a strong enzymatic resistance. A new family of α-amino-γ-lactam oligomers (Agl-βAA) obtained from conversion of /β peptide sequences are also described. Secondary structure of these molecules have been studied by NMR, FTIR, CD and XRD. These oligomers are able to adopt a stable 12-helix structure. Unexpectedly, these oligomers are soluble in aqueous mediums without any hydrophilic side chains
Shibata, Masayuki. "Studies on “kokumi” taste components in soybean seeds : Identification, content determination and efficient extraction." Kyoto University, 2018. http://hdl.handle.net/2433/233823.
Повний текст джерелаAmin, Mohamad N. "Synthesis of Amphiphilic α- and γ-AApeptides for Antimicrobial, Self-Assembly, and Mineralization Studies". Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4859.
Повний текст джерелаMathieu, Loic. "Synthèses et analyses structurales d’oligomères d’ATCs : une nouvelle famille de γ-aminoacides hétérocycliques pour la conception de foldamères". Thesis, Montpellier, 2015. http://www.theses.fr/2015MONT3514/document.
Повний текст джерелаThe work described herein is devoted to the synthesis and the structural characterization of a new family of heterocyclic constrained γ-amino acids, named ATCs (4-Amino-(methyl)-1,3-Thiazole-5-Carboxylic acids). These building-blocks are built around a thiazole ring inserted between the Cα-Cβ carbons allowing the limitation of the ζ dihedral angle value to 0°. The presence of two diversification points both on the γ asymmetric carbon and on the position 2 of the aromatic ring, allows a large structural diversification of the ATCs. Series of oligomers consisting in dimers, tetramers and hexamers soluble in halogenated solvents, alcools and water have been synthesized according to peptide chemistry. The conformations of the sequences have been studied by various NMR experiments associated to modelling studies led under NMR constraints. The ATC oligomers adopt a right 39 helical shape, owning a pitch of 11.8 Å which has been confirmed by crystallography. The helix is stabilized by a conserved hydrogen bond pattern between CO(i)…NH(i+2) occurring all along the sequence axis. Circular dichroism measures have been done to check the conformational stability of the architectures. In the second part of the manuscript, we demonstrate by NMR and theoretical computing that when included in a short peptide sequence, ATCs could act as turns. The derived application consists in optimizing the biological behaviour of the ATC moiety as a turn mimetic thanks to the design and the antibacterial evaluation of a gramicidin S analogue. Based on our knowledge about the three-dimensional structure of ATC oligomers, the last part of this work deals with our efforts to develop inhibitors of protein-protein interaction STAT6-NCoA-1
Nimmagadda, Alekhya. "Design, Synthesis, Applications of Polymers and Dendrimers." Scholar Commons, 2017. https://scholarcommons.usf.edu/etd/7430.
Повний текст джерелаZimmerman, Wendy Cherie. "Association of Pericentrin with the γ Tubulin Ring Complex: a Dissertation". eScholarship@UMMS, 2004. https://escholarship.umassmed.edu/gsbs_diss/122.
Повний текст джерелаPardossi-Piquard, Raphaëlle. "Le complexe γ-sécrétase : implications dans la régulation de l'apoptose et la dégradation du peptide amyloïde". Nice, 2005. http://www.theses.fr/2005NICE4053.
Повний текст джерелаSu, Ma. "Structure-based Design, Synthesis and Applications of a New Class of Peptidomimetics: 'Y-AA Peptides and Their Derivatives." Scholar Commons, 2018. https://scholarcommons.usf.edu/etd/7580.
Повний текст джерелаLi, Yaqiong. "Gamma AApeptides as Host Defense Peptide Mimics." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6301.
Повний текст джерелаChami, Linda. "Étude de la production du peptide amyloïde dans la maladie d'Alzeimer : régulations transcriptionnelles de la βAPP et des β- et γ-sécrétases". Nice, 2012. http://www.theses.fr/2012NICE4065.
Повний текст джерелаAlzheimer’s disease (AD) is characterized by memory loss, cognitive deficits and a loss of the patient’s autonomy. AD brains harbor senile plaques mainly composed of amyloid peptide (Aβ). This peptide likely contributes to the neurodegeneration. Aβ is produced by cleavage of its precursor βAPP by two enzymatic activities, the β- and the γ-secretase. Aβ is an important therapeutic target; we thus studied the transcriptionnal regulation of the proteins involved in its production. The transcription factor NF-κB is activated in Alzheimer’s disease. We show that NF-κB reduces Aβ production by inhibiting the transcription of βAPP and of the β- and γ-secretases. This regulation is complex, as in supraphysiological Aβ concentration, a condition close to the pathology, NF-κB is an activator of Aβ production. This suggests a positive feedback loop favoring Aβ production in pathological conditions. Neuronal death is characteristic of Alzheimer’s disease. We thus studied the regulation of Aβ production by the pro-apoptotic transcription factor p53. Our preliminary results indicate that p53 inhibits Aβ secretion. Finally we show a functional dialogue between the two secretases. Thus the γ-secretase cleavage of Notch-1 and of the epithelial and the neural cadherins regulates BACE1 transcription
Petit-Paitel, Agnès. "Étude du rôle des présénilines dans la maturation de la protéine précurseur du peptide amyloi͏̈de dans la maladie d'Alzheimer et dans la maturation du récepteur Notch-1 : une fonction controversée." Paris 7, 2002. http://www.theses.fr/2002PA077149.
Повний текст джерелаBakir, Ilyas. "Molecular studies of the γ-secretase complex activity and selectivity towards the two substrates APP and Notch". Thesis, Mälardalen University, School of Sustainable Development of Society and Technology, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-9622.
Повний текст джерелаAlzheimer Disease (AD) is the most common neurodegenerative disorder in the world. One of the neuropathological hallmarks of AD is the senile plaques in the brain. The plaques are mainly composed of the amyloid β (Aβ) peptide. Aβ is generated from the amyloid precursor protein, APP, when it is first cleaved by the β-secretase and subsequently the γ-secretase complex. The γ-secretase complex cleaves at different sites, called γ and ε, where the γ-cleavage site generates Aβ peptides of different lengths and ε-cleavage generates the APP intracellular domain (AICD). The two major forms of Aβ is 40 and 42 amino acids long peptides, where the latter is more prone to aggregate and is the main component in senile plaques. The γ-secretase complex is composed of four proteins; Pen-2, Aph-1, nicastrin and presenilin (PS). The PS protein harbours the catalytic site of the complex, where two aspartate residues in position 257 and 385 (Presenilin 1 numbering) are situated. Most Familial AD (FAD) mutations in the PS gene cause a change in the γ-cleavage site, leading to a shift from producing Aβ40 to the longer more toxic variant Aβ42. Frequently, this often leads to impairments of the AICD production. Another substrate for the γ-secretase complex is Notch. It is important to maintain the Notch signaling since an intracellular domain (NICD) is formed after cleavage by the γ-secretase complex in the membrane (S3-site) and this domain is involved in transcription of genes important for cell fate decisions.
It has been reported that certain APP luminal juxtamembrane mutations could drastically alter Aβ secretion, however their effect on AICD production remains unknown. In this study we want to analyse wether the juxtamembrane region is important for the AICD production. To gain more insight into the luminal juxtamembrane function for γ-secretase-dependent proteolysis, we have made a juxtamembrane chimeric construct. A four-residue sequence preceding the transmembrane domain (TMD) of APP (GSNK), was replaced by its topological counterpart from the human Notch1 receptor (PPAQ). The resulting chimeric vector C99GVP-PPAQ and the wildtype counterpart were expressed in cells lacking PS1 and PS2 (BD8) together with PS1wt. We observed that the chimeric construct did not alter production of AICD when using a cell based luciferase reporter gene assay monitoring AICD production. We also introduced a PS1 variant lacking a big portion of the large hydrophilic loop, PS1∆exon10, since our group has previously observed that this region affect Aβ production143. We found that the absence of the large hydrophilic loop in PS1 gave a 2-fold decrease in AICD-GVP formation from C99GVPwt compared to PS1wt. The activity of PS1wt and PS1Δexon10 using C99GVP-PPAQ as a substrate gave similar result as the C99GVPwt substrate, i.e. a 2-fold decrease in AICD-GVP formation when comparing PS1Δexon10 with PS1wt. From this data we therefore suggest that the four residues in the juxtramembrane domain (JMD) (GSNK) is not altering ε-cleavage of APP when changed to Notch1 counterpart, PPAQ. Furthermore, we also show that the 2-fold decrease in AICD-production by the PS1Δexon10 molecule is not changed between the two substrates C99GVPwt and C99GVP-PPAQ. This indicates that the luminal region of APP is not directly involved in the ε-site processing. If the luminal region is affecting processing in the γ-cleavage sites, remains however to be investigated.
Gozalo, Sara. "The Role of γс Cytokines in T Cell Development, T Cell Homeostasis and CD8+ T Cell Function: A Dissertation". eScholarship@UMMS, 2004. https://escholarship.umassmed.edu/gsbs_diss/140.
Повний текст джерелаBuggia-Prevot, Virginie. "Étude de la régulation de la β-sécrétase BACE1 et du complexe γ-sécrétase dépendant des présénilines dans la maladie d'Alzheimer : rôle du peptide amyloïde et de la voie NFkB". Nice, 2008. http://www.theses.fr/2008NICE4036.
Повний текст джерелаVasudev, 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 джерелаHaque, Mohammad Mahbubul [Verfasser]. "Enantioselective synthesis of new conformationally constrained sugar-like γ- [gamma-], δ- [delta-], {ε-amino [epsilon-amino] acids, {δ-peptides [delta-peptides] and nucleoside amino acids / vorgelegt von Mohammad Mahbubul Haque". 2006. http://d-nb.info/982215967/34.
Повний текст джерелаMehlmann, Heinz [Verfasser]. "Kombinatorische Bibliotheken und Bindungsstudien von γ-Peptiden [Gamma-Peptiden] aus Glutaminsäure-Derivaten / von Heinz Mehlmann". 2005. http://d-nb.info/978060326/34.
Повний текст джерела大磯, ユタカ, 雅史 伊藤 та 千生 大竹. "オピオイドペプチドによるバゾプレシン分泌調節に関する研究". 1991. http://hdl.handle.net/2237/12989.
Повний текст джерелаWortmann, Maria [Verfasser]. "α- [Alpha] und γ-Peptide [Gamma-Peptide] aus synthetischen Cyclohexan- und Pyrrolidin-Aminosäuren / vorgelegt von Maria Wortmann". 2000. http://d-nb.info/959562605/34.
Повний текст джерелаWanka, Lukas [Verfasser]. "γ-aminoadamantane [Gamma-aminoadamantane] carboxylic acids : orientating building blocks in peptide chemistry / vorgelegt von Lukas Wanka". 2008. http://d-nb.info/988017121/34.
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 джерелаDufour-Gallant, Julien. "Synthèse en phase solide de pyrrolo[3,2-e][1,4]diazépin-2-ones modulateurs du système urotensinergétique." Thèse, 2016. http://hdl.handle.net/1866/18417.
Повний текст джерелаThe pyrrolodiazepinones have interesting biological activities on various biological receptors, which makes them a prime target for developing new biologically active small molecules. A methodology in solution had been developed for synthesizing pyrrolo[3,2-e][1,4]diazepin-2-ones, which utilized the Pictet-Spengler condensation as the key reaction to form the diazepinone ring. Pyrrolo[3,2-e][1,4]diazepin-2-ones were found to mimic an inverse γ-turn conformation by X-ray crystallographic analysis. The methodology was subsequently implemented on three types of support: Merrifield resin, Wang resin and the soluble TAP support. The urotensinergic system plays a role in certain diseases of the cardiovascular system, such as hypertension, heart failure and atherosclerosis. The urotensinergic system is expressed in the circulatory system, excretory and central nervous systems and includes the endogenous ligands urotensin II (UII) and urotensin II-related peptide (URP), and the urotensin receptor UT. The ligands UII and human URP are composed of the respective amino acid sequences: H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH and H-Ala-c[Cys-Phe-Lys-Tyr-Trp-Cys]-Val-OH. The peptide UII is the most potent vasoconstrictor known to date. The two peptides have different biological effects and may exhibit distinct roles in certain diseases. Their common Trp-Lys-Tyr sequence is believed to play an important role in the activity of UII and URP, and has been suggested to adopt an inverse γ-turn conformation. Notably, the laboratory of Professor David Chatenet developed the UT receptor antagonist peptide urocontrin by replacing the Trp residue by biphenylalanine (Bip) in URP. A library of pyrrolo[3,2-e][1,4]diazepin-2-one analogs was thus designed to mimic the inverse γ-turn sequence and targeted against UT. The pyrrolo[3,2-e][1,4]diazepin-2-one library was designed based on the Trp-Lys-Tyr sequence of UII and URP, and Trp-Lys-Bip sequence of urocontrin. The synthesis of the pyrrolo[3,2-e][1,4]diazepin-2-one library was achieved on Wang resin. The side chain of Tyr was mimicked using tyramine, Lys and Orn were used as the basic amino acid component, and the side chain of Trp was replicated using biphenyl (as in urocontrin) 1-naphthyl and 2-naphthyl groups that were introduced by employing their respective aldehydes in a Pictet-Spengler reaction, which furnished unsaturated and saturated S- and R-pyrrolo[3,2-e][1,4]diazepin-2-ones. Evaluation of the biological activity of the pyrrolo[3,2-e][1,4]diazepin-2-ones on the UT receptor was performed in vitro and ex vivo. Tests in vitro measured binding in CHO-cells which expressed UT by employing hUII-125I as radiolabeled control. In rat aorta, ex vivo tests measured capacity to induce contraction, or modulate the contractions induced by hUII and URP. Certain R-pyrrolo[3,2-e][1,4]diazepin-2-ones caused an up to 50% reduction of the radioactive signal of hUII-125I. Pyrrolo[3,2-e][1,4]diazepin-2-ones exhibited little activity ex vivo; however, they modulated contractions induced by hUII and URP. For example, the saturated R-analog possessing lysine and a biphenyl side chain inhibited completely hUII-induced contractions of the aorta at 14 µM with a pKb of 5.54 at 4 µM, without influencing URP-induced contractions. Pyrrolo[3,2-e][1,4]diazepin-2-ones were selective for the urotensinergic system and inactive on the related receptor endothelin-1. Pyrrolo[3,2-e][1,4]diazepin-2-ones represent the first small molecules that can differently modulate the biological activities of UII and URP, and offer interesting potential as tools for studying the urotensinergic system.