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1
Michaelis, Katrin. "Design, Synthese und molekularbiologische Evaluierung synthetischer Ribonucleasen mit Cyclen-Grundgerüst." [S.l.] : [s.n.], 1999. http://deposit.ddb.de/cgi-bin/dokserv?idn=960909303.
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Kaushik, Vivek. "Synthesis of cyclen based receptors and their use in separations biotechnology." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/2611.
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A number of purification techniques such as adsorption, centrifugation, chromatography, extraction, distillation, filtration, precipitation etc. to name a few, are commonly used for the purification. However, due to a constant need of purification of even more complex crude mixtures, be it reaction mixtures, various proteins and DNA from cell extracts or medicinal compounds and fragrances from plant extracts, scientists needed to consistently develop new and improved techniques of purification. One such great advancement in the field of chromatography was the development of affinity chromatography. It revolutionized the field of bioseparations technology, and the dream of single stage purification of complex biological substrates such as proteins, enzymes, co-enzymes, DNA, RNA etc. was realized. Development of various precipitation techniques involving phase tags, acid-base induced precipitation, host-guest interactions, chemoselective precipitation etc. further simplified purification procedures for few substrates. However, only a few examples of chemoselective precipitation are known in literature.1, 2 In 2005, our group synthesized a cyclen-based receptor.9 This receptor showed very strong and very specific affinity for the pyrene based dyes (HPTS, APTS, PTA) under physiological conditions, similar to that of the natural receptors for their ligands. Upon interaction with the dye, this artificial receptor formed a low solubility complex which had micromolar stability. Various structure and activity studies established the essentiality of the macrocyclic structure of the receptor for the dye recognition. We further decided to study the effect of various substituents on the aromatic ring on the binding and quenching affinity of the receptor. A series of receptors bearing electron-withdrawing and electron-donating substituents were synthesized (receptor 4-6). We also synthesized a receptor having aliphatic groups instead of aromatic groups attached to the thiourea group (receptor 7) as well as a receptor lacking thiourea linkage (receptor 8). The results of fluorometric titrations of these receptors were consistent with the previous structure and activity studies, as the receptors having electron withdrawing nitro- and bromo substituents (receptor 4 and 6 respectively) on the aromatic groups (have increased π-stacking) were better receptor than cyclen 1. Interestingly, the receptor 5, bearing an electron-donating methoxy groups on the aromatic ring, has also shown an increase in the affinity towards HPTS. We speculated that this increased affinity could be due to the higher affinity of receptor 5 towards Na+ which was essential for the proper arrangement of the receptor binding arms. The receptor with the aliphatic chain (receptor 7) showed a complicated complexation process and showed variable fluorescence quenching at various receptor concentrations. This behaviour was probably due to the formation of complexes of a various stochiometries. Expectedly, the receptor lacking thiourea group (receptor 8) did not show any interaction.Since this receptor-dye pair formed a low solubility complex of micromolar stability upon interaction, we hypothesized that this receptor-dye pair can be used in the selective separation of substrates by chemoselective precipitation. We reasoned that if the substrate of interest can be attached to the dye, this dye-substrate conjugate then can be selectively precipitated from the reaction mixture upon addition of the receptor. We tried our concept for the separation of lactose from lactose/sucrose mixture. Being a reducing sugar, lactose was labeled with APTS dye, whereas sucrose that lacks the reducing end, remained unmodified. Application of the cyclen receptor to this mixture resulted in precipitation of APTS-lactose conjugate, leaving sucrose as the only component in the solution.10 By coupling APTS dye with lactose via an imine bond, we were able to successfully isolate unmodified lactose from the conjugate by subsequent hydrolysis of the conjugate. Next, we decided to use this dye-receptor pair in affinity chromatography. We hypothesized that if the receptor can be immobilized on some solid support then it can be specifically used as an affinity support for the substrates which are attached to the pyrene-based dyes. A new receptor with a functional group on the cyclen core was needed to immobilize the receptor on the solid support. The receptor 11 having an aromatic primary amine group was synthesized. This receptor was successfully immobilized on the NHS activated agarose resin. A series of fluorometric experiments were performed to determine the specificity and binding ability of the affinity support towards the pyrene dyes. Initial results of these experiments indicated that the affinity support was very effective as indicated by almost 95% fluorescence quench of a solution of 50 nM HPTS and affinity resin. This work has opened several new venues of research, and the applicability of this dye-receptor pair in the fields of biochemistry, pharmacology, cell biology etc. will be explored.
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Ganß, Alexander [Verfasser], and Stefan [Akademischer Betreuer] Kubik. "Neuartige supramolekulare Koordinationsverbindungen mit Cyclen- oder Cyclopeptiduntereinheiten / Alexander Ganß. Betreuer: Stefan Kubik." Kaiserslautern : Technische Universität Kaiserslautern, 2016. http://d-nb.info/1108270468/34.
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Fok, Wanyiu. "Theranostic porphyrin-cyclen gadolinium complex for photodynamic therapy and magnetic resonance imaging." HKBU Institutional Repository, 2019. https://repository.hkbu.edu.hk/etd_oa/706.
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Photodynamic therapy (PDT) and Magnetic resonance imaging (MRI) are two techniques used in therapeutic and diagnostic purpose respectively. PDT can selectively kill the cancer cells by utilizing light and photosensitizer, while MRI provides invasive imaging on our interior bodies. If these two techniques combine, the probe can act as both PDT and MRI agent at the same time. This theranostic agents can bring great efficiency in the cancer treatment. In this project, a porphyrin-cyclen gadolinium based dual functions bio-probe, PZnGdL, is designed for diagnostic and photodynamic therapeutic functions. PZnGdL demonstrated a great T1 signal enhancement for MRI, in which its T1 relaxivity is 15.06 mM-1s-1 (at 1.4T, 37oC). The T1 relaxivity is five-fold higher than the clinically approved MRI contrasting agent Gd-DOTA, (2.92 at 1.4T, 37oC). Furthermore, PZnGdL exhibits low dark toxicity and high photocytotoxicity. Therefore, its photodynamic therapeutic index (PDI) in HeLa cells is as high as 1348 upon 1 J/cm2 light irradiation. Results from the present study show that PZnGdL is an effective photodynamic therapy agent as well as a safe and promising MRI contrasting agent.
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Bernier, Nicolas. "Macrocycles en série tétraazacycloalacnes : synthèse et étude de complexation de dérivés du cyclen." Brest, 2007. http://www.theses.fr/2007BRES2018.
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Le travail consiste en la synthèse de ligands dimériques de type renforcés basés sur l’unité cyclen ainsi qu’en l’étude de leurs caractéristiques acido-basiques et de leurs propriétés complexantes vis-à-vis du cuivre (II) et de l’anion triphosphate. La voie de synthèse nécessite la mono-N et la frans-di-N-fonctionnalisation spécifique du cyclen. La stratégie développée au laboratoire, utilisant l’outil “aminal”, a été appliquée à la synthèse de quatre nouvelles familles de ligands renforcés. La méthodes est aisée et efficace. Les études préalables de protonation ont montré que les ligands dimériques renforcés présentent des propriétés fortement, voire extrêmement basiques. En conséquence, ils sont fortement chargés sur toute la gamme de pH. Les études menées en spectroscopie UV-visible et en Résonance Paramagnétique Electronique ont montré la formation des composés mono- et di-métallés pour les trois familles de ligands dimériques renforcés. Ces derniers se montrent particulièrement stables et présentent une géométrie pyramide à base carrée plus ou moins déformée, pour laquelle le ligand adopte une conformation cis-V. De plus, la présence d’interactions métal-métal a pu être détectée entre les sites paramagnétiques des complexes dimétallés. Les études de complexation de l’anion triphosphate indiquent que les ligands renforcés complexent fortement l’anion triphosphate sur toute la gamme de pH. Une forte augmentation des constantes de complexation a été observée par rapport aux dimères ne possédant pas de structure renforcée, particulièrement à pH neutre et basiqueThe project consist in the preparation of new constrained macropolycycles based on cyclen subunits and in the study of their acido-basic caracteristics and their ability to complex copper (II) and triphosphate anion. The synthesis require selective mono-N or trans-di-N-alkylation of the cyclen macrocycle. The approach developped by the laboratory using “aminal” protecting group, was applied to the synthesis of four new constrained family ligands. The method is versatile, efficient and atom economic. In protonation studies, the dimeric ligands exhibited strong or drastic basicity behaviour. Consequently, they present a high level of protonation all along the pH scale, even in basic medium. UV-visible and Electronic Paramagnetic Resonance spectra evidenced formation of mono- and di-metallic copper (II) species for all dimeric constrained macropolycycles. These complexes exhibit exceptional stabilities and present a distorded square pyramidal geometry for wich the host ligand adopt a folded cis-V conformation. Moreover, metal-metal interactions was detected between paramagnetic copper (Il) centres in dimetallic complexes. Complexation studies on triphosphate anion recognition point out that the dimeric reinforced ligands strongly interact with anionic species in all the pH scale. A strong increase of the complexation constants was observed in comparison with non constrained dimeric ligand, particularly at neutral and basic medium pH
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Walter, Jürgen [Verfasser]. "Cyclisierung von Tetraprolin : Aufbau verschiedener diastereomerer Cyclen aus D- und L-Prolin / Jürgen Walter." Ulm : Universität Ulm. Fakultät für Naturwissenschaften, 2000. http://d-nb.info/101547053X/34.
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jayasinha, arachchige Rajith Madushanka. "Solid-State NMR Structural Studies of Proteins Using Cyclen Based Paramagnetic Metal Chelating Probes." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1461765391.
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Perera-Bobusch, Chrischani [Verfasser]. "Synthesis and Biological Evaluation of Artificial Metalloproteases Based on Amphiphilic Cyclen Derivatives / Chrischani Perera-Bobusch." Berlin : Freie Universität Berlin, 2016. http://d-nb.info/109466295X/34.
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Hormann, Jan [Verfasser]. "DNA-Spaltung durch Kupfer(II)cyclen-basierte Metallonukleasen : Einfluss von Heteroatomaustausch und Interkalatorsubstitution / Jan Hormann." Berlin : Freie Universität Berlin, 2016. http://d-nb.info/1099282969/34.
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Bradbury, Adam John, and babradbury@optusnet com au. "METAL ION ACTIVATED ANION SENSORS." Flinders University. School of Chemistry Physics and Earth Sciences, 2007. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20080319.125059.
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A series of new, octadentate, fluorescent, macrocyclic ligands have been prepared with a view to using them to study aromatic anion sequestration. The eight-coordinate Cd(II) complexes of the ligands have been shown capable of acting as receptors for a range of aromatic oxoanions. This has been demonstrated by perturbation of both 1H NMR chemical shift values and the anthracene derived fluorescence emission intensity as the potential guest anion and the host are combined. Non-linear least squares regression analysis of the resulting titration curves leads to the determination of binding constants in 20% aqueous 1,4-dioxane which lie in the range 10^2.3 M-1 (benzoate) to 10^7.5 M-1 (2,6-dihydroxybenzoate). By reference to the X-ray determined structures of related, but non-fluorescent inclusion complexes, the primary anion retention force is known to arise from hydrogen bonding between the anion and four convergent hydroxy groups that exist at the base of a cavity that develops in the complexes as their aromatic groups juxtapose upon coordination. This work reveals significant stability enhancement when hydroxy groups are positioned on the anion at points where O-H...pi hydrogen bonding to the aromatic rings that constitute the walls of the cavity becomes geometrically possible.
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Pagan, Augustine J. IV. "Heterosandwich assay of nicotinic acetylcholine receptors." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3815.
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Using the technology afforded by Winschel et al., cyclen-1, a high affinity, strong complexation agent for 8-hydroxypyrene-1,3,6 trisulfonate and derivatives, a new assay has been developed for fluorescently labeling proteins of interest (POIs). Ligation of the endogenous ligand for nicotinic acetylcholine receptors (nAChRs), acetylcholine, using click chemistry afforded the triazole derivative of an alkynyl-acylcholine (compound 1) with 8-azidopyrene-1,3,6 trisulfonate (compound 2). Liposomes encapsulated with Rhodamine B were used to strengthen the initial fluorophore response of compound 2, using an anchored form of cyclen-1 complex. Using a palmitoyl tail as the lipophilic moiety for liposomal amplification, the subsequent response has a fluorophore ratio of up to 1:1 million, compound 2:Rhodamine B molecules. in vitro assay using compound 2 and cyclen-1 anchored liposomes with HEK-293 cells produced a positive binding response, allowing brightly colored fluorescent images of nAChRs upon the cellular membrane. A control for nAChR binding was performed using a co-culture of HEK-293 and endothelial cell lines. Control experiments show compound 2 and liposomes weak binding endothelial cells, however, this could be do to accumulation from another mechanism, more work is necessary to prove whether or not this is correct.
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El, Ghachtouli Sanae. "Caractérisation, étude thermodynamique et structurale de complexes tétraazamacrocycliques porteurs de groupements pyridine ou pyrazine." Reims, 2007. http://theses.univ-reims.fr/exl-doc/GED00000535.pdf.
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L’objectif poursuivi au cours de ce travail est l’étude de l’influence des paramètres structuraux de complexes mono- et bistétraazamacrocycles de cuivre et de nickel sur leurs propriétés électroniques. Les ligands développés dans ce but sont des cyclens et cyclams monoN-fonctionnalisés par des groupements de type pyridine ou des bismacrocycles basés sur des cavités cyclen ou cyclam séparées par des liens de type pyridine ou pyrazine. L’influence de la présence d’atomes coordinants exomacrocycliques sur les caractéristiques stéréochimiques et électroniques des complexes a ainsi été évaluée. Dans le cas des complexes de cyclen- et cyclam-pyridine, l’analyse radiocristallographique a permis de mettre en évidence que la sphère de coordination du métal comprend l’atome d’azote pyridinique. Dans le cas du ligand cyclam-méthylpyridine, la synthèse des complexes de nickel et de cuivre a permis d’isoler dans chaque cas deux isomères configurationnels. Leur étude électrochimique a permis de montrer que l’oxydation (pour le nickel) ou la réduction (pour le cuivre) du métal s’accompagne d’une isomérisation d’un isomère configurationnel en l’autre. Ces réarrangements topologiques ne sont possibles que grâce à la modification de degré d’oxydation de métal. Dans le cas des complexes bismacrocycliques, l’analyse radiocristallographique des complexes, lorsqu’elle a été possible, montre que les atomes d’azote des espaceurs pyridine et pyrazine participent à nouveau à la coordination du ou des centres métalliques. Ceci a pour conséquence de diminuer la distance entre métaux complexés par rapport aux complexes homologues à espaceur non fonctionnalisé. Les propriétés électroniques des complexes dinucléaires formés avec les ligands biscyclams ont été étudiées par électrochimie et RPE. L’étude électrochimique du [Ni2(biscyclam-pyridine)] a montré qu’il était à nouveau possible d’induire une isomérisation de ces complexes par changement du degré redox du métal. L’étude en RPE des complexes dinucléaires [Cu2(biscyclen-pyridine)] et [Cu2(biscyclam-pyridine)] a permis de mettre en évidence une interaction entre les électrons non appariés de chaque cation métallique. Cette interaction est d’autant plus forte que la distance métal-métal est courte. Pour les complexes dinucléaires [Cu2(biscyclen-pyrazine)]et [Cu2(biscyclam-pyrazine)], l’espaceur se comporte comme un ligand pontant entre les deux centres métalliques et selon le ligand, un chemin d’échange magnétique entre les centres métalliques peut existerIn this work, the structural parameters influence on the electronic properties of nickel and copper mono- and bismacrocyclic complexes has been evaluated. In that goal, the ligands under study were monoN-functionalised cyclen and cyclam where the pendant arm was a pyridine group and biscyclen and biscyclam where the inter-cavities spacer was a pyridine or a pyrazine linker. In particular, the influence of exomacrocyclic coordinating atoms on stereochemical and electronic complexes characteristics was studied. For cyclen- and cyclam-pyridine complexes, the X-ray crystallographic analysis has shown that the nitrogen pyridinic atom participates to the metal coordination sphere. For the cyclam-methylpyridine ligand, the complexes synthesis allowed us to isolate two configurational isomers. According to the metal, their electrochemical study has highlighted that the oxidation (for nickel) or the reduction (for copper) process is accompanied by a configurationnal isomerisation between these isomers. For the bismacrocyclic complexes, the X-ray crystallographic analysis has shown when it was possible, that the nitrogen atoms of the spacer (pyridine or pyrazine nitrogen atoms) are also coordinating. By comparison with homologous complexes where the spacer is unfunctionalised, this coordination has resulted in a shorter intermetallic distance. The dinuclear electronic complexes’ properties were then examined by electrochemistry and EPR spectroscopy. The electrochemical study of [Ni2(biscyclam-pyridine)] has highlighted an isomerisation process between two configurationnal isomeric complexes. The copper complexes [Cu2(biscyclen-pyridine)] and [Cu2(biscyclam-pyridine)] EPR study has above all evidenced an interaction between the unpaired electrons of each metal cation. This interaction is as strong as the intermetallic distance is short. For these dinuclear complexes, the spacer behaves like a bridging ligand between the two metal centers and according to the ligand, a exchange magnetic path way between the metal centers can exist
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Woinaroschy, Kristina Michaela. "Cyclen transition metal complexes as biomimetic catalysts, phosphate anion sensors and building-blocks in supramolecular assemblies." kostenfrei, 2007. http://www.opus-bayern.de/uni-regensburg/volltexte/2009/890/.
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Hodyl, Jozef Andrew Zbigniew, and jozef hodyl@flinders edu au. "Silica Immobilised Metal Ion Activated Molecular Receptors." Flinders University. School of Chemistry, Physics and Earth Sciences, 2008. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20090301.162335.
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Immobilisation of functional entities, such as, enzymes, onto solid supports, as a means of facilitating their removal from the surrounding environment and subsequent regeneration has been in practice for many decades. This work focuses on the immobilisation and analysis of three-walled (pendant armed), cyclen based receptor complexes immobilised onto a silica surface for the purpose of sequestering aromatic anions from aqueous solution: Si-GPS-[Cd(Trac)](ClO4)2, Si-GPS-[Cd(DiPTrac)](ClO4)2, and Si-GPS-[Cd(TriPTrac)](ClO4)2 were the immobilised receptors used.
Initially, synthesis of a three-walled model receptor, [Cd(TracHP12)](ClO4)2, that is not bound to silica yet mimics the properties of the silica anchored receptor complexes with a hydroxypropyl pendant arm was effected. Aromatic anion binding constant measurements were made on the model receptor using 1H NMR monitored titrations in DMSO-d6 which showed that, in comparison to the first generation four-walled receptors, the removal of one of the pendant arms did not affect the binding capability of the receptor's cavity significantly. It was shown that the binding strength correlated well with the pKa of the particular anion with, for example, p-hydroxybenzoate > m-hydroxybenzoate > o-hydroxybenzoate. The precursor to this receptor was then immobilised onto a silica surface and subjected to metal ion uptake studies to gauge its coordination properties with a number of divalent metal(II) ions: Cd(II), Pb(II), Zn(II), Cu(II) and Ca(II). The three Cd(II) coordinated receptor complexes mentioned above were then subjected to inclusion studies with a number of aromatic anions in aqueous conditions whereupon a reversal of the previously mentioned trend, i.e. o-hydroxybenzoate > m-hydroxybenzoate > p-hydroxybenzoate was observed. This indicated that the presence of water in the system changes the hydrogen bonding mode of the host-guest complexes, and was a major discovery arising from this work.
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Soibinet, Mathieu. "Complexes du cuivre (II), nickel (II) et cobalt (III) avec des ligands bis macrocycliques dérivés du cyclam et du cyclen : Synthèse, études thermodynamique et structurale." Reims, 2002. http://www.theses.fr/2002REIMS023.
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Des ligands bis-macrocycliques dérivés du cyclam ou du cyclen ont été obtenus par une nouvelle méthode de synthèse via un intermédiaire bis-cis-aminal. L'étude des propriétés thermodynamiques et structurales des complexes formés entre ces ligands et les cations cuivre(II), nickel(II) et cobalt(III) a été réalisée. En solution aqueuse, l'étude potentiométrique et spectroscopique (RPE, UV visible) des complexes du cuivre(II) a montré l'existence, selon la valeur du rapport R = [ligand]/[métal], de complexes mononucléaires ou dinucléaires de très grande stabilité. A l'état solide, les complexes dinucléaires obtenus ont été essentiellement étudiés par diffraction de rayons X et par différentes méthodes spectroscopiques (absorption X, UV visible, RPE, RMN). Des essais de complexation d'anions ont été réalisés. Seul le complexe dinucléaire Cu2-paracyclen permet d'obtenir la fixation d'anions, tels que les ions oxalate, malonate ou hexacyanoferrate(II) entre les deux centres métalliques.
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Delépine, Anne-Sophie. "Polyamines pour la reconnaissance d'anions d'intérêt biologique." Brest, 2009. http://www.theses.fr/2009BRES2009.
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Les propriétés physico-chimiques complexantes des polyamines cycliques et linéaires sont maintenant clairement établies. Elles forment en effet des complexes très stables avec les cations métalliques et peuvent interagir avec des substrats anioniques en milieu aqueux lorsque les atomes d’azote deviennent accepteurs d’électrons après protonation. Si la complexation des anions s’est développée plus lentement que celles des cations, elle est devenue un domaine de recherche à part entière dès lors que l’importance des complexes des espèces chargées négativement a été reconnue tant au niveau biologique qu’écologique. Notre travail s’inscrit dans ce contexte, et a consisté en l’étude de la complexation de polyphosphates inorganiques et organiques, plus particulièrement le triphosphate et l‘adénosine triphosphate (ATP), par des ligands di- et tri-topiques dérivés d’une tétramine cyclique, le cyclen, et de deux tétramines linéaires, la N,N’-bis(2-aminoéthyl)-l,3-propanediamine et la triéthylènetétramine, présentant un espaceur rigide aromatique de type benzène ou pyridine. Le mémoire reprend la synthèse des deux premières familles de ligands déjà connues au laboratoire. Pour notre part, l’élaboration d’une méthode de monoalkylation sélective de la triéthylènetétramine basée sur l’outil bis-aminal a permis d’élargir la gamme des dérivés polytopiques étudiés. Nous avons ensuite évalué l’effet de la basicité et de la géométrie des ligands sur la complexation de polyphosphates inorganiques et organiques ciblés par potentiométrie et RMN. Les études ont permis d’identifier les diverses forces qui régissent l’interaction ligand-substrat. Nous avons notamment pu souligner l’apport sur la coordination d’interactions η- η entre l’espaceur aromatique du ligand et l’adénine de l’ATP et le rôle d’un point d’ancrage supplémentaire constitué par l’atome d’azote du lien pyridinePhysico-chernicalproperties of cyclic and linear polyamines are now well known since they are recognized to form highly stable complexes with metallic cations, and to interact with anionic substrates in aqueous medium aller protonation of the nitrogen atoms. As for cation complexation, there is a growing interest in the molecular recognition of anionic species because of their potential applications in environmental, industrial and health-related areas. Phosphate-type anions are ubiquitous as well in human activity effluents as in biological structures. 0ur work was then devoted to the study of inorganic and organic polyphosphates complexation, especially triphosphate and adénosine triphosphate (ATP), by di- et tri-topic ligands derived from a cyclic tetraamine (cyclen), and two linear tetraamines (N,N’-bis(2-aminoethyl)-l,3-propanediamine and triethylenetetramine), linked by rigid benzyl or pyridinyl spacer. We fisrtly report the synthesis of two families of ligands previously developed in ow group, as well and we describe a third class of ligands obtained by a new easy to run selective mono-Nalkylation of triethylenetetraamine using the bisaminal tool. The effect of both basicity and geometry of these ligands on the complexation of inorganic and organic polyphosphates were then investigated using potentiometry and NMR spectroscopy. These studies allowed a better understanding of the key features governing the ligand-substrate interactions. Among them, η-stacking interactions between the aromatic spacer of the ligand and the adenine ring of ATP, and the importance of the nitrogen atom of the pyridyl spacer as additional anchoring point were proved to stabilize efficiently the host-guest complexes
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Franklin, Constance D. "A Novel Synthesis and Subsequent Decyclization of Iminothiozolidinones: Expansion of Thiourea Chemistry for Biological Applications." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4853.
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Small molecule synthesis has become a valuable tool in the study of biological systems. Biologically active compounds can be designed based on well-characterized endogenous systems or they can be found through the screening of large libraries of small molecules. This work involves the development of a small library of cyclic thiourea-based small molecules by use of an unreported synthetic pathway. Briefly, parent thioureas were cyclized by reaction with bromoacetyl bromide, and one or two isomeric heterocycles were found to form. Further studies indicated that the reaction could be easily manipulated by temperature or solvent to effectively control the product distribution. These iminothiozolidinones were characterized by single crystal x-ray analysis. The new reaction was explored in an effort to uncover the factors influencing the control of the isomer formation. Furthermore, these iminothiozolidinones underwent a novel decyclization reaction that resulted in the loss of the parent thiourea connectivity and incorporation of an external nucleophile to yield an aminooxoethylcarbamothionate. The reaction proceeds through a termolecular mechanism. These reactions can be combined to a one-pot reaction series. These compounds share similarities with a class of compounds reported to be known HIV-1 reverse transcriptase inhibitors94. In addition to these new synthetic reactions, work was conducted with a previously developed cyclen thiourea receptor for the anionic dye HPTS and its derivatives50-52. This system was used to develop a cell labeling assay that led to the amplification of fluorescent labeling of target cells through the use of liposomes. Briefly, a dye-ligand conjugate for the glycine receptor was synthesized. Liposomes functionalized with the cyclen receptor were prepared encapsulating Rhodamine B. Confocal microscopy studies demonstrated the binding of the HPTS-ligand to the cell membranes. Addition of the liposomes resulted in quenching of the green fluorescence, indicating binding of the cyclen to HPTS. Subsequent excitation of Rhodamine B showed red fluorescence associated with the cells. The intensity of the red signal was demonstrably higher than for the signal resulting from the binding of the ligand-dye to the receptor. Together, these projects increase the synthetic usefulness of thiourea based small molecules and demonstrate the potential biological applications of related compounds.
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Kulinna, Heiko [Verfasser]. "Neutral and Cationic Zirconium Alkyl and Hydride Complexes Supported by a Macrocycle Based on Cyclen : Synthesis, Characterization and Reactivity / Heiko Kulinna." Aachen : Shaker, 2013. http://d-nb.info/1051574447/34.
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Nouri, Hela. "Synthèse et caractérisations de propriétés optiques d’un nouveau ligand dérivé du Cyclen-azaxanthone : Applications potentielles dans la détection sélective du Zn2+." Thesis, Reims, 2013. http://www.theses.fr/2013REIMS018.
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Le présent travail concerne principalement l'élaboration d'un nouveau ligand en l'occurrence le cyclen-hydrazone, luminescent et efficace pour une détection relativement sélective de l'ion d'intérêt biologique, Zn2+. La synthèse du groupement azaxanthone à greffer sur le cyclen a été décrite. A partir de ces ligands, la complexation de zinc, a été traitée dans le but de développer une sonde optique sélective pour les ions métalliques de la première série de transition. Une étude photophysique associée à un travail de modélisation théorique en solution a plus particulièrement montré la formation de deux nouveaux complexes de zinc. Finalement, le contrôle des conditions de déprotection par hydrazinolyse du cyclen-glyoxal-azaxanthone, a montré que le motif azaxanthone puisse être maintenu dans la conception de nouveaux complexant de métaux de la première série de transitionThis study deals with the development of a new ligand: the cyclen-hydrazone, luminescent and effective for a relatively selective detection of biological ion, Zn2+. The synthesis of graft azaxanthone group to the cyclen was described. From these ligands zinc complexation was treated in order to develop an optical probe selective for the first row transition metals. A photophysic study associated with theoretical modeling work in solution, specifically showed the formation of two new zinc complexes. Finally, the monitoring of deprotection by hydrazinolysis of cyclen-glyoxal-azaxanthone, showed that the azaxanthone deprotection could be maintained in the design of new metals complexes of the first serie of transition metals
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Gupta, Deepshikha. "NEW APPROACHES TO CYCLOPENTADIENYL-FUSED THIOPHENE COMPLEXES OF IRON and SYNTHESIS AND CHARACTERIZATION OF CARBONIC ANHYDRASE ACTIVE-SITE MIMICS FOR CO2 HYDRATION." UKnowledge, 2018. https://uknowledge.uky.edu/chemistry_etds/92.
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Polyheterocycles such as polythiophene and its derivatives comprise an important class of conducting polymers used for electronic applications. They have been of great interest for use in electronic materials due to their increased environmental stability as well as novel electronic properties in their polymer states. We have been interested in exploring the electronic properties of organometallic analogues of the low-band-gap polymer poly(benzo[3,4-c]thiophene) (polyisothianaphthene) that incorporates η5-cyclopenta[c]thienyl monomers such as ferroceno[c]thiophene. First chapter of this dissertation involved synthetic attempts to ferroceno[c]thiophene. Exploring a shorter synthetic route to starting material, 1,2-di(hydroxymethyl)ferrocene was the first task. This was followed by attempts to synthesize an important precursor, 1,3-dihydroferroceno[c]thiophene to our target molecule, ferroceno[c]thiophene. In order to achieve our target precursor molecule, 1,3-dihydroferroceno[c]thiophene, we reacted 1,2-di(hydroxymethyl)ferrocene with H2S/H2SO4 and Na2S/HBF4 respectively. Reaction of 1,2-di(hydroxymethyl)ferrocene with either H2S/H2SO4 or Na2S/HBF4 results in 2,16-dithia[3.3](1,2)ferrocenophane instead of monomeric 1,3-dihydroferroceno[c]thiophene. Dehydration of 1,2-di(hydroxymethyl)ferrocene with dilute H2SO4 resulted in 2,16-dioxa[3.3](1,2)ferrocenophane. Formation of the five-membered tetrahydrothiophene or tetrahydrofuran rings is probably disfavored compared to formation of the ten-membered ferrocenophane rings because of greater strain in the five-membered rings. Thus, in order to achieve our target molecule ferroceno[c]thiophene, we took an alternate route. We decided to pursue the route with 1,4-dihydro-2,3-ferrocenodithiin being the precursor to our final target molecule. This was successfully accomplished. 1,2-Di(hydroxymethyl)ferrocene reacts with thiourea in the presence of catalytic trifluoroacetic acid to give a water-soluble thiouronium salt, which reacts with aqueous potassium hydroxide in air to give 1,4-dihydro-2,3-ferrocenodithiin, via oxidation of the intermediate 1,2 di(mercaptomethyl)ferrocene. 1,4-dihydro-2,3-ferrocenodithiin, an important precursor to our desired heterocyclic chemistry was synthesized.
The increased emission of CO2, a greenhouse gas, to the atmosphere is a matter of serious worldwide concern. Every year a few gigatons of CO2 are added to the atmosphere by various anthropogenic activities like burning of fuel for electricity, running industry and transportation. Thus, developing ways to reduce the emission of CO2 to the atmosphere is of major importance. Although the amine-based absorption method is considered the most reliable, it is an expensive alternative. The catalyzed enhancement of CO2 absorption is a critical component to reduce the capital cost of CO2 capture. Specifically, an effective catalyst will increase the CO2 hydration rate, thereby decreasing the size of the absorber tower needed. In biological systems, CO2 hydration is catalyzed by the enzyme carbonic anhydrase, which contains ZnII in its active site. Carbonic anhydrase typically is not stable enough to be used in an industrial process, therefore, there is a need to synthesize robust, inexpensive CO2 hydration catalysts.
Majority work of this dissertation focuses on designing catalysts that show high CO2 hydration rate similar to carbonic anhydrase while showing superiority towards temperature, pH and inhibitors. We focused our efforts on complexes of Zn, Cu and Co with ligands such as 1,4,7,10-tetraazacyclododecane (cyclen), 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane (teta and tetb), tris(benzimidazolylmethyl)amine (BIMA) and anionic tris(pyrazolylborate)s that mimic the enzyme, carbonic anhydrase. Several of these complexes have been reported for their interesting CO2 capture properties but they contain hazardous perchlorate ion. We desired to replace them with benign, non-coordinating counterions like PF6-, BF4-, Cl-, CH3COO-, NO3-, CF3SO3-, SiF62- that avoid the potentially explosive perchlorate salts. In order to test the activity of synthesized catalysts under industrial capture conditions, we designed a quick experimental screening pH drop method. [[Zn(cyclen)(H2O)][SiF6]•2H2O as well as a number of other catalysts have been synthesized and tested for their post-combustion CO2 capture enhancement capabilities in aqueous solvent mixtures under both pH-drop screening and stopped-flow conditions.
[Zn(cyclen)(H2O)][SiF6]•2H2O, which has an unreactive counteranion, is found to catalyze CO2 hydration in aqueous solvent mixtures under both pH-drop screening and stopped-flow conditions. However, under pH-drop which has conditions similar to industrial post combustion capture, activity of Zn(cyclen)(H2O)][SiF6]•2H2O drops as compared to observed in stopped-flow conditions probably because of bicarbonate coordination to Zn active site in these systems. The Zn center is highly electron deficient and therefore easily coordinates anions, inhibiting the ability to reform hydroxyl species on the metal. Thus, we decided to test the catalysis of benchmark enzyme carbonic anhydrase under similar conditions to determine the threshold value. Carbonic anhydrases catalyze the hydration of carbondioxide at ambient temperatures and physiological pH with the highest known rate constant= 106 M–1 s–1, but in our system (CAER pH drop screening) came out to be 438797 M–1 s–1. The lower catalytic rate constant for carbonic anhydrase in 0.1000 M K2CO3, similar to Zn-cyclen, strengthens the conjecture that at high bicarbonate concentrations, HCO3– binding to the Zn(II) active site slows catalysis by inhibiting bicarbonate displacement with water to regenerate the active species.
The complexes containing anionic ligands that donate electron density into the metal center may serve to remove anionic bicarbonates/carbamates from the secondary coordination sphere and away from the metal center, thereby facilitating bicarbonate/anion dissociation and increasing CO2 hydration rates. We studied catalysis of trispyrazolylborate molecule in 30% MEA and found the molecule to be catalytically active. We also developed an NMR-based method to see if the coordination of solvents to CO2 capture solvents can be studied.
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Lynch, Jonathan D. "Breaking the Organic Mold: Introducing Copper into the Influenza A Arena with Neutral and Divalent Complexes." BYU ScholarsArchive, 2020. https://scholarsarchive.byu.edu/etd/8677.
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Influenza A (IVA) continues to pose a growing global threat even as current medications are becoming less effective. One of the main avenues of research into new anti-IVA drugs is its homotetrameric Matrix 2 proton channel (M2A), without which the virus would be unable to release its viral RNA into the host cell. The drug amantadine used to bind and block M2A until near-ubiquitous resistance formed as an M2A-S31N mutation, starting around 1995 and proceeding to 2005 when amantadine was disallowed for use as an anti-IVA drug. The standard organic structure currently being used for M2A inhibitor research comprises an adamantyl foot group, a heterocyclic aryl body group, and a cyclic head group. A sample set of compounds with this standard structure was compared and reviewed, focusing on positive and negative moieties and modifications. Modifications on the foot group were all more or less detrimental, body groups with two heteroatoms were advantageous, and larger head groups appeared better. Four other scaffolds known to literature were proposed for further study due to beneficial aspects of each. Where most anti-M2A research deals exclusively with organic compounds, metals and their potential in drugs have been almost entirely ignored due to the increased toxicity they bring. Free copper was found in past research to be the only first-row transition metal to show significant M2A-inhibitory activity, proposed to do so by binding the H37 cluster that acts as a pH-dependent control switch for the channel. Six overall-neutral copper complexes were synthesized as a combination of amantadine, cyclooctylamine, and null scaffolds with two of either acetate or acetamide arms as chelators. The complexes were found to block both M2A-WT and M2A-S31N. Along with CuCl¬¬2, though, they had little to no effect on M2A-H37A, providing confirming evidence that the copper binds at the H37 tetrad. Only one complex, Cu(cyclooctylamineiminodiacetate), outperformed CuCl2 in channel block studies and efficacy against two IVA strains, but all of the complexes were found to have lower cytotoxicity. Because M2-H37 is highly conserved, these complexes show promise for further testing against all strains of influenza A. Five net-divalent copper complexes were then synthesized with multiple aza or amine groups as chelators. The complexes failed to show any significant activity against M2A, however, which was thought to be due to size or polarity rejection or electromagnetic repulsion. One of the ligands, though, an adamantyl derivative of a tetraaza macrocycle, was a novel compound, and its copper complex, along with two others, were unknown to the CCDC database. The three complexes were characterized by X-ray diffraction and discussed.
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Bonnet, Christine. "Un motif sur la cycline B nécessaire à l'activation de CDK1 chez la levure ?" Paris 6, 2002. http://www.theses.fr/2002PA066509.
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Asrar, Ahmad Malik. "Testing the cell cycle phase specificity of cyclins: can an earlier cyclin trigger a later event?" Doctoral thesis, Universitat Autònoma de Barcelona, 2013. http://hdl.handle.net/10803/127221.
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Progression through the cell cycle is directed by cyclin dependent kinases (CDKs), which are essential for normal and cancer cell proliferation. CDKs are activated by association with cyclins specific to each cell cycle phase (G1, S, G2, and M). Thus, CDK associated with G1 phase cyclins promote the expression of proteins necessary for DNA replication, but is unable to activate it. CDK associated with S phase cyclins, in turn, triggers the activation of chromosomal origins of replication, but is unable to promote chromosome condensation and segregation of sister chromatids, which is carried out by CDK associated with mitotic cyclins.
Despite the essential role of CDKs in cell cycle progression, how the different cyclins promote specifically the various processes of the cell cycle was still an open question by the time this thesis was initiated. Since the discovery of cyclins by Nobel laureate Tim Hunt [Evans et al. (1983) Cell 33:389] it was assumed that cyclins confer substrate specificity. However, later on, fellow Nobel laureate Paul Nurse proposed an alternative quantitative model, [Stern & Nurse (1996) Trends Genet 12:345], based on the observation that successive waves of cyclins result in increased levels of CDK activity. While low levels of activity (CDK associated with G1 cyclins) are sufficient promote progression through the G1 phase and start the pro-S phase transcription program, would be unable to trigger replication. Moderate levels of activity (CDK associated with S phase cyclins) would be able to activate replication but not mitosic events, which would require the high CDK activity associated with M phase cyclins.
If correct, the quantitative model should fulfill two predictions, but only one was demonstrated by the Nurse lab. Eukaryotic unicellular yeast cells are able to survive with a single mitotic cyclin, which is notwithstanding able to orderly drive the cell through the different cell cycle phases [Fisher & Nurse (1996) EMBO J 15:850]. Therefore M-CDK activity is able to promote the previous phases of the cycle in the fission yeast Schizosaccharomyces pombe However, if a purely quantitative mechanism applies, the complementary prediction should be true as well: an early cyclin to be able to trigger later events if expressed at levels high enough.
To test such prediction we generated a budding yeast Saccharomyces cerevisiae strain carrying a G1 cyclin G1 resistant to degradation, under a strong inducible promoter, and fused to a nuclear localization signal. Our results show that one such cyclin is capable of firing chromosome replication conditions in which the S phase cyclins, G2 and M are suppressed. Therefore, our results support the quantitative model against the requirement of substrate specificity. How eukaryotic cells prevent premature activation of the critical cell cycle processes that lead to genomic instability, seems therefore trust in the regulation of activity levels and limiting the presence of cyclin at specific time and space.
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Waclaw, Ronald Raymond. "Expression of cell cycle regulatory proteins cyclin B1, cyclin E, and cdk2 during the first three cell cycles of preimplantation mouse embryo development using indirect immunofluorescence." Virtual Press, 1999. http://liblink.bsu.edu/uhtbin/catkey/1125042.
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The cell cycle is a highly regulated process driven by endogenous factors that have regulatory functions. Certain proteins such as cyclins and cyclin-dependent kinases (cdks) are needed to progress through the four phases of the cell cycle. Cell cycle regulatory proteins have been characterized in somatic cells and exhibit phase specific expression patterns. However, the changes in expression of these proteins have not been characterized in early cleavage stage mouse embryos. This study utilized indirect immunofluorescence microscopy to determine the expression pattern of cell cycle regulators cyclin B 1, cyclin E, and CDK2 during the first three cell cycles of preimplantation mouse embryo development. Results suggest unique and specific patterns of expression for all three cell cycle regulators at different stages of the cell cycle. In G1 of the first cell cycle, cyclin E is expressed at high levels, whereas cyclin B 1 and CDK2 are expressed at moderate levels. During DNA synthesis (S phase), CDK2 levels slightly increase. However, cyclin B 1 and cyclin E levels begin to decline in S and continue to decrease to minimal levels in G2. CDK2 expression follows a similar trend during G2, decreasing considerably. During the second cell cycle, cyclin B 1 and CDK2 show staining patterns similar to the first cell cycle. The expression of cyclin E is maintained at a moderate level throughout the entire second cell cycle. Cyclin B 1, cyclin E, and CDK2 are all expressed at moderate levels during GI of the third cell cycle. During S phase, cyclin B 1 and CDK2 are maintained at moderate levels, but cyclin E is decreased to minimal levels. The expression of all three proteins was minimal during G2. This study provides baseline information on the unique expression patterns of cell cycle regulators in early mouse embryos. The determination of cell cycle protein expression will allow for a better understanding of the complex mechanisms in the division process during preimplantation mouse embryo development.Department of Biology
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Bhaduri, Samyabrata. "Regulation of CDK1 Activity during the G1/S Transition in S. cerevisiae through Specific Cyclin-Substrate Docking: A Dissertation." eScholarship@UMMS, 2014. http://escholarship.umassmed.edu/gsbs_diss/871.
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Several cell cycle events require specific forms of the cyclin-CDK complexes. It has been known for some time that cyclins not only contribute by activating the CDK but also by choosing substrates and/or specifying the location of the CDK holoenzyme. There are several examples of B-type cyclins identifying certain peptide motifs in their specific substrates through a conserved region in their structure. Such interactions were not known for the G1 class of cyclins, which are instrumental in helping the cell decide whether or not to commit to a new cell cycle, a function that is non-redundant with B-type cylins in budding yeast. In this dissertation, I have presented evidence that some G1 cyclins in budding yeast, Cln1/2, specifically identify substrates by interacting with a leucine-proline rich sequence different from the ones used by B-type cyclins. These “LP” type docking motifs determine cyclin specificity, promote phosphorylation of suboptimal CDK sites and multi-site phosphorylation of substrates both in vivo and in vitro. Subsequently, we have discovered the substrate-binding region in Cln2 and further showed that this region is highly conserved amongst a variety of fungal G1 cyclins from budding yeasts to molds and mushrooms, thus suggesting a conserved function across fungal evolution. Interestingly, this region is close to but not same as the one implicated in B-type cyclins to binding substrates. We discovered that the main effect of obliterating this interaction is to delay cell cycle entry in budding yeast, such that cells begin DNA replication and budding only at a larger than normal cell size, possibly resulting from incomplete multi-site phosphorylation of several key substrates. The docking-deficient Cln2 was also defective in promoting polarized bud morphogenesis. Quite interestingly, we found that a CDK inhibitor, Far1, could regulate the Cln2-CDK1 activity partly by inhibiting the Cln2-substrate interaction, thus demonstrating that docking interactions can be targets of regulation. Finally, by studying many fungal cyclins exogenously expressed in budding yeast, we discovered that some have the ability to make the CDK hyper-potent, which suggests that these cyclins confer special properties to the CDK. My work provides mechanistic clues for cyclinspecific events during the cell cycle, demonstrates the usefulness of synthetic strategies in problem solving and also possibly resolves long-standing uncertainties regarding functions of some cell cycle proteins.
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Houriet-Segard, Geneviève. "Logement, cycles démographiques et cycle de vie." Paris, Institut d'études politiques, 1998. http://www.theses.fr/1998IEPP0029.
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Cette thèse comprend trois approches du marché du logement dont l'objectif est de saisir les interactions entre démographie et logement. 1. Analyse de l'influence des cycles démographiques sur la demande agrégée de logement : une revue de modèles macroéconomiques de marché du logement incluant un déterminant démographique est présentée, puis une modélisation du marché du logement est effectuée sur la base de données économiques françaises. L'hypothèse majeure de ce modèle est l'idée d'un surplus systématique d'offre de logement par rapport à la demande dont l'ampleur détermine le prix. Enfin, ce modèle est simulé selon différents scenarios démographiques et économiques. 2. Analyse des déterminants démographiques des choix individuels de logement : le but est de déceler une éventuelle logique de cycle de vie dans les comportements résidentiels des ménages avec acquisition d'un logement pendant la période d'activité et désaccumulation pendant la retraite. Ces comportements sont testés sur l'enquête logement 92: la consommation de logement, le statut d'occupation et la mobilité sont analyses. 3. Microsimulation du marché du logement qui permet d'étudier les interactions entre le vieillissement de la population, le marché du logement et les transferts intergénérationnels (legs et système de retraite) : le modèle considère une population hétérogène ou les individus naissent, ont des enfants, vieillissent et meurent, reçoivent des salaires ou retraites et bénéficient parfois d'un héritage. Chaque agent vit une ou deux périodes pendant lesquelles il optimise sa consommation selon les principes de la théorie du cycle de vie généralisée. Alors que l'on se retrouve à chaque période avec une population d'individus aux caractéristiques différentes, le bouclage macroéconomique du modèle met en place un système de prix qui assure la cohérence comptable des comportements. Ce modèle est enfin simulé afin d'analyser les effets de différents chocs démographiques et évolutions économiquesThis thesis includes three parts. It's objective is to better understanding interactions between demography and housing. Analysis of the demographic cycles influencing the housing demand and the housing market equilibrium: some existing housing market's models with a demographic determinant are reviewed. Such a model is then built up based on French economical data. The model's main hypothesis is that there is a systematic excess of housing supply over demand. The level of this excess has a direct incidence on the price of housing. This model is simulated using various demographic and economical scenarios. Analysis of residential choices during the life cycle: the focus is the household's housing behavior with the saving's life cycle theory (e. G. People buy a house when they are working and sell it when they are retire to compensate the loss of revenue and to maintain the same level of consumption). These behaviors are tested on the data of the French survey "enquete logement 92". Behaviors such as the housing consumption, the tenure choice and the mobility of elder householders are tested in the context of saving's life cycle theory. Microsimulation of the housing market that allows the study of the interactions between aging population, the housing market and intergenerational transfers (bequests and social security programs): at the microeconomic level, this model takes into account a heterogeneous population simulating events such as birth's and death's dates, salary, retirement pension and sometimes inheritances. All people live two periods in their lifetime where they will optimize their consumption following the generalized saving's life cycle theory. Lastly, individual behaviors are aggregated and compiled at a macroeconomic level. This model is also simulated for different demographic and economical evolutions
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Martinsson, Hanna-Stina. "Single cell analysis of checkpoints in G₁ /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-455-4/.
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Ji, Jun-Yuan. "Functions of Cdk1-cyclin B in regulating the early embryonic mitoses in Drosophila /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/5124.
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Bockstaele, Laurence. "Réévaluation de la régulation de l'activité de la CDK4, kinase dépendante des cyclines D, clé de l'engagement dans le cycle cellulaire: rôle de l'inhibiteur p27." Doctoral thesis, Universite Libre de Bruxelles, 2006. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210626.
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La progression à travers le cycle cellulaire est assurée par l’activation séquentielle d’une série de complexes cycline-CDK. Les complexes cycline D-CDK4 assurent la progression au cours de la phase G1 du cycle cellulaire en phosphorylant les protéines « antioncogéniques » de la famille Rb. L’activation de la CDK4 nécessite son association à une cycline D et sa phosphorylation sur Thr172 par la CAK nucléaire (CDK activating kinase). Le rôle essentiel des protéines de la famille Cip/Kip dans la régulation de l’activité de ces complexes reste controversé. Les protéines de cette famille (comprenant p27 et p21) ont initialement été identifiées comme des inhibiteurs puissants des complexes cycline-CDK et comme les intermédiaires de l’action antimitogénique de différents signaux intra ou extra-cellulaires. Il a été proposé que la liaison de la p27 ou de la p21 aux complexes cycline D-CDK4 empêche leur phosphorylation activatrice par la CAK et leur activité pRb kinase. Cependant, l’observation que des complexes cycline D-CDK4 associés à p21/p27 possèdent une activité pRb kinase a donné naissance à une seconde hypothèse sur la régulation de ces complexes par la p27 ou la p21. Ces « inhibiteurs » ont été paradoxalement proposés comme facteurs nécessaires et suffisants d’assemblage et de localisation nucléaire des complexes cycline D-CDK4. Dans le modèle physiologiquement relevant des thyrocytes de chien en culture primaire, la mitogénèse dépendante de l’AMPc activée par la TSH diffère des cascades des facteurs de croissance puisqu’elle n’induit pas les cyclines D mais au contraire augmente l’accumulation de l’«inhibiteur» de CDK p27. L’AMPc stimule l’assemblage des complexes cycline D3-CDK4, leur translocation nucléaire et leur association à p27. Dans ce modèle, le TGF&61538; inhibe la mitogénèse dépendante de l’AMPc en inhibant la translocation nucléaire des complexes cycline D3-CDK4 et leur association à la p27.Nous avons étudié l’activité catalytique et l’activation des complexes cycline D3-CDK4-p27 issus des thyrocytes de chien en culture primaire ou produits en cellules d’eucaryotes supérieurs (CHO et Sf9). Nous avons pu montrer que les complexes cycline D3-CDK4-p27 issus des thyrocytes de chien stimulés par la TSH présentent une activité pRb-kinase qui est inhibée par le TGF&61538; En outre, la production des complexes cycline D3-CDK4-p27 en cellules CHO ou Sf9 nous a permis de montrer que l’impact de la p27 sur l’activité catalytique des complexes cycline D3-CDK4 dépend de sa stoechiométrie de liaison à ces complexes. L’analyse du profil de séparation par électrophorèse bidimensionnelle de la CDK4 issue de ces trois systèmes montre que la p27 n’empêche pas la phosphorylation activatrice de la CDK4, même aux concentrations de p27 qui empêchent l’activité pRb kinase du complexe cycline D3-CDK4. Nous avons également montré dans les cellules CHO que la p27 détermine la localisation nucléaire des complexes cycline D3-CDK4, ceux-ci étant relocalisés dans le cytoplasme par la transfection d’un mutant de la p27 dépourvu de son signal de localisation nucléaire. Ces résultats valident les observations réalisées par immunofluorescence dans les thyrocytes de chien dans lesquels nous avons mis en évidence une étroite corrélation au niveau des cellules individuelles stimulées par la TSH entre la translocation nucléaire de la CDK4 et l’apparition de la p27 nucléaire. Cette colocalisation est partiellement inhibée par le TGF&61538; Ces observations renforcent l’hypothèse d’un rôle de la p27 dans l’ancrage nucléaire des complexes cycline D3-CDK4.
Alors que la localisation de la CAK est considérée comme exclusivement nucléaire et son activité catalytique constitutive, nous avons pu montrer que la phosphorylation activatrice de la CDK4 associée à la cycline D3 n’est pas affectée par sa localisation sub-cellulaire et qu’elle est régulée par le TGF&61538; dans les thyrocytes de chien et par le sérum dans les cellules T98G indépendamment de l’association de la CDK4 à la p27. De plus, la phosphorylation de la CDK4 sur Thr172 dans les cellules T98G est stimulée par le sérum, alors que la phosphorylation activatrice de la CDK6, son homologue fonctionnel, ne l’est pas. La comparaison de la séquence de ces deux CDKs à proximité des Thr phosphorylées (Thr177 pour la CDK6) révèle, outre une forte similarité de séquence, une différence au niveau de l’acide aminé situé en aval de la thréonine :il s’agit d’une proline dans la CDK4 et d’une sérine dans la CDK6. La mutation P173S de la CDK4 abolit la phosphorylation sur Thr172 et l’activité de la CDK4 associée à la cycline D3 dans les cellules CHO, mais n’affecte pas la phosphorylation et l’activation de la CDK4 par la CAK recombinante in vitro. L’ensemble de ces résultats suggère que la/les CAKs régulée(s) responsables de l’activation de la CDK4 n’ont pas encore été identifiées et que la proline située en aval de la Thr172 de la CDK4 est essentielle pour sa phosphorylation activatrice et son activité pRb kinase.
Doctorat en sciences biomédicales
info:eu-repo/semantics/nonPublished
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Erlandsson, Fredrik. "Immunofluorescence studies on the cell cycle expression of cyclin A and cyclin E /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-809-2/.
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Swanton, Robert Charles. "Viral cyclin disruption of mammalian cell cycle control mechanisms." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286205.
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Doare-Michel, Nola. "Relations entre cycle de développement familial et cycles d'identité." Université Claude Bernard - Lyon I, 1994. http://www.theses.fr/1994LYO1M292.
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Datar, Sanjeev Ashok. "Developmental regulation of growth and cell cycle progression in Drosophila melanogaster : a larval growth arrest screen, and molecular and genetic analysis of the cyclin D/Cdk4 complex /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/5008.
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Zhang, Hong. "Involvement of Cdk/cyclin motif in ciliate cell cycle regulation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0015/NQ56653.pdf.
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Ford, Jack Ragnar. "Cyclin dependent kinases and cell cycle control in Trypanosoma brucei." Thesis, University of Glasgow, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312512.
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Brunner, Benjamin. "The sulfur cycle: from bacterial microenvironment to global biogeochemical cycles /." Zürich : [s.n.], 2003. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=15197.
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Powell, Brian Edward. "The influence of minor cycles on low cycle fatigue crack growth." Thesis, University of Portsmouth, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354380.
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Fatigue crack propagation rates have been measured for two titaniumbased aeroengine disc alloys using compact tension test pieces. The loading block employed simulates two features of the engine flight pattern. A major stress cycle represents the start-stop operation which leads to low cycle fatigue. In-flight vibrations, which may give rise to high cycle fatigue, are represented by superimposed minor cycles of high frequency. This combined loading is applied in a specially developed test facility consisting of an electromagnetic vibrator mounted above a servohydrau1ic actuator. When the minor cycles are inactive the fractographic cracking processes are those associated with major cycle crack growth. Once active, the minor cycle growth may either generate extensive cyclic cleavage or increase the separation of the fatigue striations associated with the periodic major cycles. The contribution of the minor cycles to the total growth rate is dependent on their relative number and size. In gas turbine and compressor discs and blades, components which experience large numbers of minor cycles per flight, the damage associated with active minor cycles is dominant. Consequently, the onset of minor cycle damage effectively determines the useful life of such components. The threshold values associated with the minor cycles have been used to predict the onset of minor cycle activity. Similarly the method of linear superposition has been used to predict the subsequent fatigue crack growth rates. These predictions are successful for Ti-6Al-4V, whilst for Ti-5331S they are either found to be accurate or safe. Although Ti-5331S displays a marginally greater resistance to the onset of minor cycle crack growth, of greater significance is its reduced crack growth rates prior to this event. As a consequence components fabricated from Ti-5331S will exhibit longer fatigue crack propagation lives when subjected to the conjoint action of high and low cycle fatigue.
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Campo, Woytuk Nadia. "Curious Cycles: Feminist Probes for Cultivating Curiosity of the Menstrual Cycle." Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-254985.
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Curious Cycles responds to the tensions that arise when designing technologies for menstruation and menstrual cycles, touching upon notions of curiosity, noticing, sharing, taking or making space, and our relationships with our bodies and their fluids. The project follows a Research through Design approach, guided by Soma Design and feminist research methods. Curious Cycles are a set of cultural probes; objects and interactions designed to gather experiences and insights from ve people who menstruate, throughout the duration of a cycle (approximately one month). The objects are meant to "cultivate curiosity", provoking reections on the ways we currently relate to our bodies and bodily uids and speculating on how we might relate to them in the future. This work seeks to approach the design method of cultural probes from a feminist perspective and contributes through the concept of "cultivating curiosity", a way to design menstrual cycle technologies by attending closely to the changing social and material experiences of the body, which in turn can challenge the cultural taboos surrounding menstruation.Curious Cycles svarar mot spänningarna som uppkommer när teknologier designas för menstruation och menstruationscykeln, genom idéer kring nykenhet, att märka, att dela med sig, att ta eller göra plats, och våra relationer med våra kroppar och deras vätskor. Projektet följer en Research through Design metodik, guidad av Soma Design och feministiska forskningsmetoder. Curious Cycles är en uppsättning cultural probes; föremål och interaktioner designade för att samla erfarenheter och insikter från fem menstruerande personer genom deras hela menstruationscykel (vilka pågår cirka en månad). Föremålen är menade att kultivera nykenhet för att framkalla reektioner kring de sätt vi för närvarande relaterar till våra kroppar och kroppsliga vätskor på, och även för att spekulera kring hur vi kan relatera till de i framtiden. Detta arbete närmar sig cultural probes från feministiska perspektiv och bidrar med konceptet "cultivating curiosity", ett sätt att designa teknologier för menstruationscykeln genom att ingående uppmärksamma förändringar av sociala och materiella erfarenheter av kroppen, vilket i sin tur kan utmana kulturella tabun kring menstruation.
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Horton, Lynn Elizabeth. "Studies on cyclin structure and pRb phosphorylation in cell cycle control." Case Western Reserve University School of Graduate Studies / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=case1057684343.
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Prasad, Aarathi. "Cell cycle regulation through the D-Type cyclins." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405947.
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Ekholm-Reed, Susanna. "The role of cyclin E in cell cycle regulation and genomic instability /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-894-7/.
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Puyol, Marta. "Cell cycle and cancer : the role of cyclin dependent kinases in tumourigenesis." Thesis, Kingston University, 2009. http://eprints.kingston.ac.uk/20409/.
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Most human cancers carry mutations in cell cycle regulators that result in deregulated Cdk activity, which can either be amplification of the cyclins, elimination of the Cdk inhibitors or mutations in the Cdks. These modifications have a high prognostic value. Cdk2 activity has been shown to be upregulated in different kind of tumours (mammary and prostate carcinomas, and lymphomas) due to the mutation of its regulators, p27KiP1 and cyc/in E; and this alteration has a high prognostic value. Moreover, an insensible INK4 point mutation in Cdk4 has been described in human melanomas. To evaluate the importance of Cdks in neoplastic development, the loci encoding Cdk4, Cdk6 and Cdk2 were ablated to study the effect of Cdk deficiency in tumour development. To this end, the corresponding Cdk knock out mice were crossed with the K_Ras+/LSLG12V;RERertert strain that carries an endogenous K-Ras oncogene whose expression is dependent on Cre-mediated recombination. Postnatal expression of this oncogene leads to the development of lung adenomas and adenocarcinomas. Primary MEFs derived from K- Ras+ILSLG12V;RERrrtlert embryos lacking either Cdk4, Cdk6 or Cdk2 displayed decreased proliferation in culture and prevented the growth in low serum condition. However, no obvious differences were detected in immortal MEFs regardless of the missing Cdk.
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Chow, Jeremy Pak Hong. "Inhibitory phosphorylation of cyclin-dependent kinases in normal cell cycle and checkpoints /." View Abstract or Full-Text, 2003. http://library.ust.hk/cgi/db/thesis.pl?BICH%202003%20CHOW.
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Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003.Includes bibliographical references (leaves 127-148). Also available in electronic version. Access restricted to campus users.
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Kernen, Joakim. "Trends, cycles and institutions : -Job polarization and the business cycle in Europe." Thesis, Uppsala universitet, Nationalekonomiska institutionen, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-367063.
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This thesis studies the cyclical aspect of job polarization in Europe. Contributions include offering a comparison to the findings of previous research on the United States, and extending the analysis by introducing labor market institutions. The analysis is done in two parts, first showing that the observed link between job polarization and jobless recoveries in the US is observed in Europe, but not across all countries and business cycles. In Scandinavia, the process of job polarization appears smoother than the spurts observed in the US. The second part involves regression analyses of the relationship between labor market institutions, the business cycle and occupational employment. The results indicate that stricter labor market institutions are less robustly associated with Routine employment than other occupational groups and that Routine employment is more sensitive to the business cycle than other types of employment. Further, rigid labor market institutions may prevent some of the Routine decline associated with economic downturns, while not necessarily affecting the long run employment. Limitations of the analysis regards rough estimates of the key variables, number of observations and the lack of identification associated with cross-country analyses.
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Plesca, Dragos Costin. "Cyclin E provides a link between Cell Cycle, DNA Repair and Apoptosis." Kent State University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=kent1208492093.
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Lindqvist, Arne. "Regulation of CDK dephosphorylation in mitotic entry /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-362-0/.
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Williams, Lisa Marie. "Cell cycle inhibitors in control of chronic gammaherpesvirus infection /." Connect to abstract via ProQuest. Full text not available online, 2007.
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Thesis (Ph.D. in Microbiology) -- University of Colorado Denver, 2007.Typescript. Abstract available online via ProQuest Digital Dissertations. Includes bibliographical references (leaves 207-223).
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Lundgren, Andreas. "The ABC of the cell cycle: roles of the mammalian Cdc25 isoforms /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-639-5/.
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Yang, Chen. "Thermodynamic Cycles using Carbon Dioxide as Working Fluid : CO2 transcritical power cycle study." Doctoral thesis, KTH, Tillämpad termodynamik och kylteknik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-50261.
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The interest in utilizing the energy in low‐grade heat sources and waste heat is increasing. There is an abundance of such heat sources, but their utilization today is insufficient, mainly due to the limitations of the conventional power cycles in such applications, such as low efficiency, bulky size or moisture at the expansion outlet (e.g. problems for turbine blades). Carbon dioxide (CO2) has been widely investigated for use as a working fluid in refrigeration cycles, because it has no ozonedepleting potential (ODP) and low global warming potential (GWP). It is also inexpensive, non‐explosive, non‐flammable and abundant in nature. At the same time, CO2 has advantages in use as a working fluid in low‐grade heat resource recovery and energy conversion from waste heat, mainly because it can create a better matching to the heat source temperature profile in the supercritical region to reduce the irreversibility during the heating process. Nevertheless, the research in such applications is very limited. This study investigates the potential of using carbon dioxide as a working fluid in power cycles for low‐grade heat source/waste heat recovery. At the beginning of this study, basic CO2 power cycles, namely carbon dioxide transcritical power cycle, carbon dioxide Brayton cycle and carbon dioxide cooling and power combined cycle were simulated and studied to see their potential in different applications (e.g. low‐grade heat source applications, automobile applications and heat and power cogeneration applications). For the applications in automobile industries, low pressure drop on the engine’s exhaust gas side is crucial to not reducing the engine’s performance. Therefore, a heat exchanger with low‐pressure drop on the secondary side (i.e. the gas side) was also designed, simulated and tested with water and engine exhaust gases at the early stage of the study (Appendix 2). The study subsequently focused mainly on carbon dioxide transcritical power cycle, which has a wide range of applications. The performance of the carbon dioxide transcritical power cycle has been simulated and compared with the other most commonly employed power cycles in lowgrade heat source utilizations, i.e. the Organic Rankin Cycle (ORC). Furthermore, the annual performance of the carbon dioxide transcritical power cycle in utilizing the low‐grade heat source (i.e. solar) has also been simulated and analyzed with dynamic simulation in this work. Last but not least, the matching of the temperature profiles in the heat exchangers for CO2 and its influence on the cycle performance have also been discussed. Second law thermodynamic analyses of the carbon dioxide transcritical power systems have been completed. The simulation models have been mainly developed in the software known as Engineering Equation Solver (EES)1 for both cycle analyses and computer‐aided heat exchanger designs. The model has also been connected to TRNSYS for dynamic system annual performance simulations. In addition, Refprop 7.02 is used for calculating the working fluid properties, and the CFD tool (COMSOL) 3 has been employed to investigate the particular phenomena influencing the heat exchanger performance.QC 20111205
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Zhu, Xi-Ning. "Regulation of cyclin dependent kinase inhibitors during the vertebrate cell cycle : a dissertation /." San Antonio : UTHSC, 2007. http://proquest.umi.com/pqdweb?did=1324370261&sid=1&Fmt=2&clientId=70986&RQT=309&VName=PQD.
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