Rozprawy doktorskie na temat „Dissociation constant of inhibitor”
Utwórz poprawne odniesienie w stylach APA, MLA, Chicago, Harvard i wielu innych
Sprawdź 44 najlepszych rozpraw doktorskich naukowych na temat „Dissociation constant of inhibitor”.
Przycisk „Dodaj do bibliografii” jest dostępny obok każdej pracy w bibliografii. Użyj go – a my automatycznie utworzymy odniesienie bibliograficzne do wybranej pracy w stylu cytowania, którego potrzebujesz: APA, MLA, Harvard, Chicago, Vancouver itp.
Możesz również pobrać pełny tekst publikacji naukowej w formacie „.pdf” i przeczytać adnotację do pracy online, jeśli odpowiednie parametry są dostępne w metadanych.
Przeglądaj rozprawy doktorskie z różnych dziedzin i twórz odpowiednie bibliografie.
Mann, Maretta Clare, i n/a. "Sialylmimetics as Potential Inhibitors fo Vibrio Cholerae Sialidase". Griffith University. Institute for Glycomics, 2004. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20061006.083947.
Pełny tekst źródłaMann, Maretta Clare. "Sialylmimetics as Potential Inhibitors fo Vibrio Cholerae Sialidase". Thesis, Griffith University, 2004. http://hdl.handle.net/10072/367187.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Full Text
Sooväli, Lilli. "Spectrophotometric measurements and their uncertainty in chemical analysis and dissociation constant measurements /". Online version, 2006. http://dspace.utlib.ee/dspace/bitstream/10062/627/5/soovalililli.pdf.
Pełny tekst źródłaRonneburg, Henrike [Verfasser], Jürgen [Akademischer Betreuer] Dittmer i Kurt [Akademischer Betreuer] Engeland. "Prognostische Relevanz von Rho-GDP dissociation inhibitor Proteinen beim Mammakarzinom / Henrike Ronneburg. Betreuer: Jürgen Dittmer ; Kurt Engeland". Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2009. http://d-nb.info/1024895807/34.
Pełny tekst źródłaEvangelista, Jaqueline Pesciutti. "Selenoproteínas: Seril-tRNA Sintetase e as selenoproteínas do Trypanosoma brucei". Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-13112014-171709/.
Pełny tekst źródłaSelenocysteine (Sec) amino acid is the major biological form of selenium and requires a complex molecular machinery for its synthesis and co-translational incorporation into selenoproteins. The Seryl-tRNA synthetase (SerRS) starts this biosynthesis and matches the tRNASec (SELC) with a serine and the tRNAsSer, therefore the focus of this study is on SerRS of Trypanosoma brucei (T. brucei) and tRNAsSer and SELC interactions, with fluorescence anisotropy techinic to determinat dissociation constants. Three selenoproteins, namely SelT, SelK and SelTryp, besides the route of selenocysteine synthesis there be in Kinetoplastidae. DNA fragments that coding for these selenoproteins were subcloned in 28a and 29a to use into Escherichia coli (E. coli) cells. For Selk and SelTryp proteins, the expression protocol did not show an unsatisfactory result to continue the experiments. Many difficulties were encountered in studies with Selt protein, mainly in attempts to make it soluble. Our analyses revealed SelT was a membrane protein, therefore it could cause changes in some objectives and search for new strategies. It could be expressed and purified in cromatographis. SEC-MALLS assays showed a stability of the protein detergent complex. With TbSerRS is possible to conclude that the organization of binding specificity of the enzyme with its ligands occurs increasingly: SelC>tRNASer7>tRNASer3a>tRNASer3b. And selenoproteins in T. brucei, it is necessary for new constructions to SelK and SelTryp to continue the experiments trying to crystallizes SelT, since prototolo for obtaining the protein-detergent complex is assembled and stabilized.
Karbanová, Kateřina. "Disociační chování přírodních biokoloidů". Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2017. http://www.nusl.cz/ntk/nusl-316163.
Pełny tekst źródłaViktorinová, Jana. "Využití chronopotenciometrické titrace v huminovém výzkumu". Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2013. http://www.nusl.cz/ntk/nusl-216933.
Pełny tekst źródłaChaudhury, Chaity. "Identification and biochemical characterization of a novel receptor:ligand interaction between FcRn and albumin". The Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1110211148.
Pełny tekst źródłaSmallman, Matthew John. "Spatial regulation of Rho GTPase signalling during root hair development in Arabidopsis thaliana is reliant upon the guanine nucleotide dissociation inhibitor SCN1". Thesis, University of Bristol, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496221.
Pełny tekst źródłaLi, Muchen. "Determination of dissociation constant of DNA/DNA hybridization by three different surface techniques : comparison of surface plasmon resonance, fluorescent microarray and evanescent field fluorescence". Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEC028/document.
Pełny tekst źródłaBiosensors are powerful detection and analysis tools that have been widely applied in pharmaceuticals, healthcare, biomedical research, and environmental monitoring. However different biosensors use different transducers and therefore different substrates and surface chemistries. All of these parameters may have an effect on the biomolecular reactions at the interface and lead to a deviation in dissociation constant Kd measurements. In this context, this PhD work aimed at comparing three different techniques: fluorescent microarray, evanescent field fluorescence biosensor and surface plasmon resonance (SPR) biosensor, to determine DNA hybridization Kd. For the classical fluorescence microarray, the substrate is a glass slide and the detection is performed at the end of the experiment. In the case of evanescent field fluorescence biosensor, polystyrene is the substrate and it permits a real-time detection. SPR is performed on thin gold film. It is a real-time and a label-free technique. The two fluorescent based techniques require to label the targets with fluorescent dyes prior to the measurements. One important factor determining the performance of the analysis is the surface chemistry of the sensor chip. Herein, we have optimized gold surface chemistry for thiol modified DNA grafting. We studied two cleaning methods: piranha solution and oxygen plasma, aiming at obtaining a clean gold surface without oxidation of the gold. Then, we optimized SPR assay parameters such as interfacial structure of sensor chip, ionic strength... After, these three techniques were used to measure the DNA hybridization Kd. The results showed that the Kds measured are similar for the three techniques. In addition, increasing surface probe density resulted in an increase of Kd of DNA hybridization
Truttmann, Anita Carmen. "Apparent MG[hoch]2plus-Adenosine 5-Triphosphate dissociation constant measured with Mg[hoch]2plus-Macroelectrodes under conditions pertinent ot [hoch]31P NMR ionized magnesium determinations /". [S.l.] : [s.n.], 1997. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
Pełny tekst źródłaMEDA, PHILIPPE. "Etude de la liaison de la tubuline au centrosome". Université Joseph Fourier (Grenoble), 1996. http://www.theses.fr/1996GRE10189.
Pełny tekst źródłaAnnala, Suvi Katariina [Verfasser]. "FR900359, an inhibitor of guanine nucleotide dissociation, effectively blunts signaling of GTPase-deficient Gq : mechanism of action and relevance for treating Gq-driven cancers / Suvi Katariina Annala". Bonn : Universitäts- und Landesbibliothek Bonn, 2019. http://d-nb.info/1194464807/34.
Pełny tekst źródłaMartins, Nádia Helena. "Ensaios enzimáticos de proteases de HIV-1 de subtipos brasileiros". Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-27042008-122417/.
Pełny tekst źródłaDespite years of intense research around the world, HIV continues to represent considerable therapeutical challenge. In order to gain more insights into resistance of polymorphic mutations of existing HIV subtypes toward commercially available pharmaceutics, we studied inhibition of subtypes B and F HIV proteases (PRs) [native and two mutant enzymes clinically identified in Brazilian patients] by six commercial inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir). Our results show that all these inhibitors have significantly higher Ki values for the subtype F HIV PR (Fwt) and both mutant enzymes than that for the B subtype HIV PR (Bwt). Furthermore, the biochemical fitnesses of these proteases, or their vitalities, are also considerably higher than that of Bwt. The accumulation of commonly detected resistant mutations in HIV PRs with natural polymorphisms turns Fwt sufficiently catalytically active to guarantee the virus viability and confers it a large degree of cross resistance against all studied inhibitors.
Obame, Nkoghe Germain. "Synthèse et étude cinétique de l'homolyse de biomolécules utilisables comme agents théranostiques". Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4367.
Pełny tekst źródłaThis work is presented in 2 parts. The first part is dedicated to the stereocontrolled synthesis of 2 series of carbonucleosides of methylenecyclopropane structure. The target molecules are analogs of entecavir, a prodrug used in triple therapy to fight against HBV. The syntheses of the carbonucleosides targets of the series I use a common chiron, an alcohol obtained by enzymatic desymmetrization of meso-diol. For example, the chemical transformation of this key intermediate allows to obtain carbonucleoside (+)-16 in 8 steps as crucial steps involving a Curtius rearrangement and the construction of the uracil base with 23% overall yield. The carbonucleoside belonging to the series II was first synthesized in 10 steps involving a reaction of Mitsunobu, a chemical acylation. Howerer the enzymatic desymmetrization of a meso-diol did not get the target carbonucleoside in an enantiopur form. The second part is dedicated to the activation and the homolysis of the alcoxyamines for a theranostic application. The synthesis of the model alcoxyamine is made from vinyl pyridine and nitroxide SG1. Activation is carried out by protonation, oxidation, methylation and benzylation of the pyridyl part and highlights the importance of polarity. It allowed getting highly labile species that release an alkyl radical and nitroxide SG1, with notably higher kd dissociation constant values and therefore activation energies Ea lower compared to the alcoxyamine not enabled
Le, Bonniec Bernard. "Contribution à l'études des sérine protéases de la coagulation et de la fibrinolyse". Paris 6, 1986. http://www.theses.fr/1986PA066414.
Pełny tekst źródłaSuchá, Šárka. "Studium acidobazických a elektrolytických vlastností hyaluronanu v roztoku". Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2015. http://www.nusl.cz/ntk/nusl-217088.
Pełny tekst źródłaMahé-Gouhier, Nicole. "Etude des interactions lipase/colipase par chromatographie d'affinite conventionnelle (cac) et haute performance (cahp)". Paris 7, 1987. http://www.theses.fr/1987PA077062.
Pełny tekst źródłaPavanelli, Jéssyca Cristine. "Modularidade gênica das famílias da dissulfeto isomerase proteica e do inibidor da dissociação de guanina: estudos computacionais, moleculares e funcionais". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-06022017-153111/.
Pełny tekst źródłaRedox pathways are important regulators of homeostasis and cell signaling, but the understanding of the mechanisms of these processes is incomplete. Thiol proteins such as protein disulfide isomerase (PDI) can be modulators of these pathways. PDI (PDIA1) is the prototype of the family of PDIs whose canonical function is a redox protein folding in the endoplasmic reticulum. In addition, PDI exerts regulatory NADPH oxidase, the main sources of cellular oxidant, and is required for activation RhoGTPases, cytoskeletal organization and migration of vascular cells. In the study of mechanisms by which regulates PDI RhoGTPases, we showed in computer networks and co-imunoprecitation experiments association between PDIA1 and the regulator of RhoGTPases, RhoGDI?. In addition, we identified strong proximity of the genes encoding these proteins. In this study, we characterize the profile and implications of this synteny. .A bioinformatic analysis by programs Ensembl, NCBI and UCSC shows a pattern of synteny between different isoforms of these two families: PDIA1 (P4HB), PDIA2 (PDIP) and PDIA8 (Erp27) are neighbors , respectively RhoGDIalfa, and RhoGDIy RHOGDIbeta with corresponding intergenic regions 7.1, 2.9 and 0:14 kb in different chromosomes of H. sapiens. The pattern of this synteny was strongly maintained in C. elegans, some fish and evenly amphibians, reptiles, birds and mammals. Yeasts express on the same chromosome, but in distant places (i.e macrosintenia) orthologs of PDIA1 and RhoGDI?, but do not express other syntenics PDIs and RhoGDIs in complex eukaryotes. However, synteny between PDI and RhoGDI was also observed in the plant A. thaliana, no evidence of a common ancestor. The syntenic pairs are associated with the stored neighboring blocks, but different for each pair, while each block contains a gene encoding a regulator of distinct PP1 (protein phosphatase-1). Phylogenetic analysis showed similar topology between the two famílias. The identified binding sites common transcription factors between different pairs, which mainly indicated ontology development, metabolic and immune response. The study of possible functional implications of synteny showed that manipulations of PDIA1 protein expression do not promote consistent change in protein expression RhoGDI, both in vitro (silencing of PDI by siRNA and overexpression of inducible lentiviral vector) and in vivo (transgenic mice overexpressing constitutive of PDIA1). The study of possible functional implications of synteny showed that manipulations of PDIA1 protein expression do not promote consistent change in protein expression RhoGDIalfa, both in vitro (silencing of PDI by siRNA and overexpression of inducible lentiviral vector) and in vivo (transgenic mice overexpressing constitutive of PDIA1). However, changes of gene expression of both genes in the intima of mouse carotid arteries during remodeling induced by flow were strongly correlated. Immunoprecipitation experiments and co-location to confocal microscopy suggested physical interaction between PDIA1 and RhoGDIAalfa. Thus, these data show an intriguing pattern of evolutionary conservation of gene proximity between POIs and RhoGDIs not common in eukaryotes. sintênicos genes often encode proteins that tend to interact physically and / or functionally. Indeed, our data suggest co-regulation and physical interaction between PDIA1 and RhoGDIAalfa, supporting the convergence of these proteins as a possible mechanism involved in redox regulation of cytoskeleton by PDIA1
Adamczyk, Katrin. "Ultrafast charge transfer processes in solution". Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2010. http://dx.doi.org/10.18452/16202.
Pełny tekst źródłaThe reaction pathways and dynamics of photoinduced bimolecular charge transfer reactions are characterised with ultrafast polarisation-sensitive UV-pump/IR-probe-spectroscopy. Generally accepted models for bimolecular electron transfer reactions suppose that charge separation in polar solvents leads to two geminate ion pairs, namely loose (LIPs) and tight ion pairs (TIPs). By monitoring vibrational marker modes TIPs and LIPs can be distinguished spectroscopically. However, multiple time scales for the formation of TIPs and LIPs indicate that a distinction between two kinds of ion pairs with well-defined geometries is a considerable simplification. TIPs and LIPs should rather be regarded as limiting cases, as there is a continuous distribution of different ion pairs between these two limits. The crucial parameter governing the nature of the ion pairs is the distribution of neutral reaction pairs subsequent to initiation of the reaction. Furthermore, TIPs are found to be highly anisotropic, revealing the importance of mutual orientation of the reactants. This thesis also presents for the first time femtosecond infrared spectroscopic results proving the existence of carbonic acid in aqueous solution. A photoacid is used to optically trigger the ultrafast protonation of bicarbonate. Carbonic acid has only been detected as solid existing in ice matrices and in the gas phase, so far. Because carbonic acid is often postulated as intermediate between carbon dioxide and bicarbonate its characterisation is of substantial support in understanding fundamental acid-base chemistry of carbonates in aqueous solution as well as in biophysical situations. Analysing the time-dependent signals using a theoretical model to describe bimolecular reaction dynamics an on-contact proton transfer reaction rate is derived. This gives an insight into the acid-base chemistry of carbonic acid.
Norberg, Daniel. "Quantum Chemical Studies of Radical Cation Rearrangement, Radical Carbonylation, and Homolytic Substitution Reactions". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8178.
Pełny tekst źródłaDebord, Jean. "Relation structure chimique-activité biologique pour quelques phosphoramides et benzamides". Poitiers, 1988. http://www.theses.fr/1988POIT2331.
Pełny tekst źródłaCheleski, Juliana. "Planejamento de inibidores da enzima diidroorotato desidrogenase de Trypanosoma cruzi por biocalorimetria". Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/75/75131/tde-19052011-110337/.
Pełny tekst źródłaDentro desse contexto, este trabalho representa uma importante contribuição para o entendimento das razões moleculares da ação farmacológica de substâncias químicas bioativas de interesse à farmacoterapia da doença de Chagas. Ao nível molecular, a enzima pertencente à via de síntese de novo de nucleotídeos de pirimidinas, diidroorotato desidrogenase do Trypanosoma cruzi (TcDHODH), é um alvo promissor para a descoberta e desenvolvimento de candidatos a fármacos de interesse para o tratamento da doença de Chagas.
Os conceitos e ferramentas da química medicinal computacional, tais como os ensaios virtuais in silico, foram usados para a identificação de inibidores da TcDHODH. Vinte e seis substâncias inéditas como inibidores da TcDHODH foram adquiridos comercialmente e avaliados experimentalmente através da Calorimetria de Titulação Isotérmica (ITC) para a determinação do mecanismo de inibição e da constante cinética de afinidade (Kiapp).
Na etapa de docagem molecular, o objetivo era identificar moléculas que apresentassem uma boa afinidade pelo sítio ativo da enzima TcDHODH. A primeira série de ligantes selecionados dos métodos in silico, apresentou inibição enzimática na concentração de micromolar com eficiência média de ligante de 0,50 kcal mol-1 átomo-1. Devido à baixa massa molecular (aproximadamente 200 kDa) e a alta eficiência de ligante, essa série foi considerada como constituída de excelentes substâncias com elevado poder de reconhecimento biomolecular. Por isso, foram caracterizadas como substâncias passíveis de otimização no processo do-ligante-para-substância matriz.
As enzimas TcDHODH e DHODH de Leishmania major (LmDHODH) têm sítios ativos com elevado grau de similaridade. Portanto, usando a enzima LmDHODH como padrão de substituição da TcDHODH é possível fazer a descrição do modo de interação do co-complexo TcDHODH-inibidor. O modo de ação descrito através da resolução da estrutura cristalográfica de raios-X, além de validar ortogonalmente os resultados cinéticos obtidos por ITC - que identificou as substâncias como inibidores competitivos (por interação direta no sítio ativo da enzima TcDHODH), geraram hipóteses farmacofóricas para a busca de novas moléculas (chamadas de segunda geração), agora com padrão superior de reconhecimento molecular do sítio da TcDHODH. Para validar complementarmente a hipótese, foi demonstrado que os inibidores da TcDHODH inibem, similarmente, a LmDHODH.
Uma análise cuidadosa da estrutura tridimensional da enzima TcDHODH, demostrou a possibilidade de ocupação do sítio S2 que se estende além da região do sítio catalítico S1, permitindo assim o aumento da afinidade biomolecular com os inibidores. Além disso, o sítio S2 não é encontrado na estrutura da proteína de humanos (HsDHODH), podendo ser uma região passível de seletividade frente à enzima TcDHODH.
O emprego adequado dessa hipótese resultou na otimização dos ligantes identificados previamente para substâncias mais potentes que inibiram a enzima de forma competitiva em relação ao substrato diidroorotato (DHO) em valores Kiapp de 121 ± 14 nM e 190 ± 10 nM.
A técnica de ITC foi fundamental no processo de descoberta de inibidores enzimáticos, pois se mostrou extremamente susceptível à determinação da interação intermolecular enzima-inibidor, permitindo acompanhar a cinética da reação e obter os valores da constante de afinidade de maneira precisa e acurada. Com isso, a taxa de acerto obtida nesta tese foi de 46%, considerando-se apenas as substâncias com valores de Ki app < 100 µM. Esse é um número favoravelmente apreciável, já que na literatura ele gira em torno de 1-10% quando o planejamento in silico é realizado, quando comparado às taxas de acerto dos métodos de ensaio em larga escala (HTS), entre 0-2 %, os resultados alcançados neste trabalho são ainda mais significativos.
Além disso, as substâncias químicas selecionadas através da integração de métodos in silico e biocalorimétricos apresentam elevado grau de complexidade no processo biomolecular de interação enzima-ligante, que permite classificá-las para as fases seguintes da gênese planejada de fármacos.
American trypanosomiasis or Chagas disease, caused by the haemoflagellate Trypanosoma cruzi, is a tropical disease that affects millions of people in Latin America. Epidemiology of Chagas disease in non-endemic countries is attained by immigration as the disease also affects people in the United States, Canada, Europe, Australia and Japan. However, the United States are not to be written off as an area of nonendemicity for Chagas disease like Europe or Asia because the southern states have enzootic T. cruzi transmission that involves triatomine species and hosts such as raccoons, opossums, and domestic dogs. Even though, this disease has been considered as a super-neglected from the big Pharma Industry viewpoint since the only available drugs for its treatment were introduced in the market more than forty years ago and worsen is that they have low efficacy and cause various severe side effects.
Although the current clinical scenario is of course discouraging and is far from being even a soothing treatment for those who suffer from the disease, it prompt ones to set efforts towards the need of discovering and developing new efficacious and safe drugs to treat Chagas disease.
Our research group covers the concept of enzymes acting as targets for the action of drugs. Once T. cruzi has many druggable targets, the dihydroorotate dehydrogenase enzyme (TcDHODH) that belongs to the de novo pyrimidine nucleotide synthetic pathway has been chosen for the search of new inhibitors that may be of use in the treatment of Chagas disease. To accomplish with this and considering that inhibitors are molecules that decrease enzyme activity leading to parasite death, we used the concepts and tools of modern computational medicinal chemistry such as in silico screening of small molecules that bind to the active site of the TcDHODH.
After a thoroughly program of virtually screening thousands of compounds, 26 were purchased from commercially available sources and experimentally assayed against the TcDHODH using Isothermal Titration Calorimetry (ITC) in order to determine the mechanism of inhibition and the kinetic affinity constant (Kiapp).
The first series of inhibitors selected from our in silico strategy were evaluated by ITC to yield compounds that inhibited the TcDHODH in the micromolar concentration range with an average of 0.50 kcal mol-1 atom-1 ligand efficiency (LE). Because the assayed compounds have low molecular weight (ca. 200 kDa) and high LE, which bring them to the specific bimolecular pattern recognition all of them were considered good inhibitors capable of being selected to enter the hit-to-lead optimization process.
The detailed description of the ligand-enzyme mode of binding (MOB) is thoroughly accomplished by solving the X ray crystal structure of the surrogate Leishmania major DHODH enzyme (LmDHODH), which has a high degree of similarity with the enzyme TcDHODH. The MOB credited to be in the active site of the TcDHODH orthogonally validated the ITC kinetic experimental data obtained for all ligands as competitive inhibitors that interact at the active site of the TcDHODH and helped to generate pharmacophoric hypotheses for the search of new second generation molecules acting against the enzyme TcDHODH. Analyzing the 3D structure of the TcDHODH along with its surrogate LmDHODH, we envisaged the possibility of compounds to extend their side chain beyond the region of the catalytic site (called S1), and interacting in a region called S2, so to increase binding affinity. Moreover, the TcDHODH S2 site that is not found in the 3D protein structure of humans (HsDHODH) is likely to offer new insights for the search of inhibitors whose binding to this S2 site can pave the roads towards the needed structural basis for selective inhibition of TcDHODH.
The most potent compounds inhibited the enzyme competitively with respect to the substrate dihydroorotate (DHO) at Kiapp values of 121 ± 14 nM and 190 ± 10 nM, which constitutes high affinity TcDHODH inhibitors. The ITC technique was pivotal to this process of enzyme inhibitors discovery, because it proved to be extremely sensitive thus allowing to monitor the kinetics of the reaction and to obtain precise and accurate values of affinity constants.
The hit rate obtained in this work, considering only those compounds with Kiapp < 100 µM, was 46%. This is a really high number, since literature values range from 1 to 10% when the planning new inhibitors via in silico methods when compared to the success rates obtained by the methods of testing on large scales (HTS), 0-2 %, the results achieved in this work are even more significant. Moreover, the compounds selected through the integration of in silico and calorimetric methods showed a high degree of complexity in the process of bimolecular enzyme-ligand recognition, which allows to pass them to the next phase of the drug design process.
Gottschalk, Ingo. "Chromatographic Studies of Solute Interactions with Immobilized Red Blood Cells and Biomembranes". Doctoral thesis, Uppsala University, Department of Biochemistry, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2668.
Pełny tekst źródłaSpecific and non-specific interactions of solutes with immobilized biomembranes were studied using chromatographic methods. Liposomes, proteoliposomes and red blood cell (RBC) membrane vesicles were immobilized by a freeze-thawing procedure, whereas whole RBCs were adsorbed in the gel beds using electrostatic interaction, binding to wheat germ agglutinin (WGA) or the streptavidin-biotin interaction.
Superporous agarose gel with coupled WGA was the most promising matrix for RBC adsorption and allowed frontal chromatographic analyses of the cells for about one week. Dissociation constants for the binding of cytochalasin B and glucose to the glucose transporter GLUT1 were determined under equilibrium conditions. The number of cytochalasin B-binding sites per GLUT1 monomer was calculated and compared to corresponding results measured on free and immobilized membrane vesicles and GLUT1 proteoliposomes. This allowed conclusions about the protein´s binding state in vitro and in vivo.
Partitioning of drugs into biomembranes was quantified and the system was suggested as a screening method to test for possible intestinal absorption of drug candidates. We also studied how membrane partitioning of drugs is affected by the presence of integral membrane proteins or of charged phospholipids.
An attempt to combine the theory for specific binding and membrane partitioning of solutes in a single equation is briefly presented.
DEGORRE, CECCALDI FRANCOISE. "Synthese, structure, proprietes physicochimiques et etude "in vitro" du pouvoir reactivateur de nouveaux antidotes de l'acetylcholinesterase inhibee par des organophosphores". Paris 6, 1988. http://www.theses.fr/1988PA066182.
Pełny tekst źródłaLagerquist, Hägglund Christine. "Affinity-, Partition- and Permeability Properties of the Human Red Blood Cell Membrane and Biomembrane Models, with Emphasis on the GLUT1 Glucose Transporter". Doctoral thesis, Uppsala University, Department of Biochemistry, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3525.
Pełny tekst źródłaThe human glucose transporter GLUT1 is abundant in red blood cells, the blood-brain barrier and epithelial cells, where it mediates the transport of the energy metabolite, glucose. In the present work some properties of GLUT1, including affinity binding of both substrates and inhibitors, transport rates as well as permeabilities of aromatic amino acids and drug-membrane interactions were analyzed by chromatographic methods.
Reconstitution by size-exclusion chromatography on Superdex 75 from a detergent with a low CMC that provides monomeric GLUT1 was examined regarding D-glucose- and CB binding as well as D-glucose transport. Upon steric immobilization in Superdex 200 gel beads, residual detergent could be washed away and dissociation constants in the same range as reported for binding to GLUT1 reconstituted from other detergents were obtained. The transport rate into the GLUT1 proteoliposomes was low, probably due to residual detergent. Binding to GLUT1 at different pH was analyzed and the affinity of glucose and GLUT1 inhibitors was found to decrease with increasing pH (5–8.7). The average number of cytochalasin B-binding sites per GLUT1 monomers was, in most cases, approximately 0.4. GLUT1 may work as a functional monomer, dimer or oligomer. To determine whether GLUT1 was responsible for the transport of the aromatic amino acids tyrosine and tryptophan, uptake values and permeabilities of these amino acids into liposomes and GLUT1 proteoliposomes were compared to the permeabilities of D- and L- glucose in the same systems. Dihydrocytochalasin B was identified to be a new inhibitor of tyrosine and tryptophan transport into red blood cells. Ethanol turned out to inhibit the specific binding between CB and GLUT1 and also to decrease the partitioning of CB and drugs into lipid bilayers. A capacity factor for drug partitioning into membranes that allows comparison between columns with different amount of immobilized lipids was validated, and turned out to be independent of flow rate, amount of lipids and drug concentration in the ranges tested.
Gong, Yun. "Structure-property relationships of dyes as applied to dye-sensitized solar cells". Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/275007.
Pełny tekst źródłaNeubauer, Svetlana. "Untersuchungen von inter- und intramolekularen Interaktionen des globalen Regulators AbrB und dessen Antirepressors AbbA". Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2014. http://dx.doi.org/10.18452/16887.
Pełny tekst źródłaIn previous binding studies it could be demonstrated that a global regulator AbrB and the extensive phyC promoter region of Bacillus amyloliquefaciens FZB45 interact in a complex manner. AbrB binding is a multistep cooperative process. The integrity of both binding sites, ABS1 and ABS2, which are separated by 162 bp, is crucial for the AbrB-mediated repression of phyC. This work presents the first real-time binding kinetics of the AbrB-DNA interaction using surface plasmon resonance (SPR). AbrB exhibited high affinities to all analyzed 40-bp oligonucleotides that were derived from the ABSs of phyC. All parts of the ABS2, but only a small region within ABS1, were bound cooperatively to AbrB with a stoichiometry of 2 DNA to 1 AbrB tetramer and with 2
Tsai, Lily, i 蔡苓莉. "A human rab GDP-dissociation inhibitor homolog from Trichoderma koningii G-39. Sequencing and analysis". Thesis, 1994. http://ndltd.ncl.edu.tw/handle/34943280901841870491.
Pełny tekst źródłaGulbrandsen, Ann Cecilie, i Thor Martin Svartaas. "INFLUENCE OF MELTING RATE ON THE DISSOCIATION OF GAS HYDRATES WITH THE KINETIC INHIBITOR PVCAP PRESENT". 2008. http://hdl.handle.net/2429/1072.
Pełny tekst źródłaRay, Paresh Chandra. "Measurement Of Dissociation Constant (Ka) And Partition Coefficient (KP) Of Weak Organic Acids From Their First Hyperpolarizabilities". Thesis, 1996. http://etd.iisc.ernet.in/handle/2005/1731.
Pełny tekst źródłaJeřábková, Kateřina. "Vliv dlouhodobého podávání morfinu na opioidní receptory v mozkové kůře potkana". Master's thesis, 2012. http://www.nusl.cz/ntk/nusl-307435.
Pełny tekst źródłaGulbrandsen, Ann Cecilie, i Thor Martin Svartaas. "INFLUENCE OF FORMATION TEMPERATURE AND INHIBITOR CONCENTRATION ON THE DISSOCIATION TEMPERATURE FOR HYDRATES FORMED WITH POLY VINYL CAPROLACTAM". 2008. http://hdl.handle.net/2429/1071.
Pełny tekst źródłaChu, Chi-Shuen, i 朱祁舜. "β2-glycoprotein I is involved in the up-regulation of Rho guanine nucleotide dissociation inhibitor-α in Huh7 cells". Thesis, 2005. http://ndltd.ncl.edu.tw/handle/89350256785856709970.
Pełny tekst źródła國立陽明大學
生物化學研究所
93
Beta-2-glycoprotein I (β2-GPI) is a human plasma protein mainly produced by the liver. Although various pathological properties have been attributed to this protein, its biological role and intracellular distribution still remain unclear. In our previous study, β2-GPI was proved to protect cells from apoptosis in J774A.1 macrophages and human coronary artery smooth muscle cells (HCASMCs) treated with nitric oxide donors. The aim of this study was to investigate the proteomic profile in β2-GPI over-expressed cells, and to clarify the role of β2-GPI in apoptosis. The differentially expressed proteins in the β2-GPI over-expressed Huh7 cells were analyzed by the two dimension gel electrophoresis analysis and subsequent MALDI-TOF / Q-TOF. We identified a β2-GPI upregulated-protein, Rho guanine nucleotide dissociation inhibitor-α (RhoGDI-α), as the Rho family protein regulator. Rac1 activity seemed to be down-regulated by RhoGDI-α in the β2-GPI over-expressed Huh7 cells. Overexpression of β2-GPI was also shown to result in reorganization of filamentous-actin (F-actin) in Huh7 cells under confocal microscopic observation. In addition, the contribution of β2-GPI to apoptosis was investigated in Huh7 hepatoma cells treated with TNF-α by cell viability assay, Hoechst33258 staining, and detection of caspase-3 and poly(ADP-ribose)- polymerase (PARP). This study shows the involvement of β2-GPI in the regulation of RhoGDI-α, Rac1, F-actin organization, and apoptosis. The result may lay the foundation for future refinements in the exploration of novel function of β2-GPI.
Suchý, Miroslav. "Fyzikálně chemické vlastnosti léčiv". Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-345322.
Pełny tekst źródłaOu, Yung, i 區永. "To investigate the role of arginine methylation of Rho GDP dissociation inhibitor α (RhoGDIα) in megakaryocytic differentiation of K562 cells". Thesis, 2013. http://ndltd.ncl.edu.tw/handle/74531624675471808738.
Pełny tekst źródła國立陽明大學
生物藥學研究所
101
Megakaryocytes are the precursors of platelets and thus play an essential role in blood clotting. K562 is a human leukemia cell line that can be induced by PMA (phorbol 12-myristate 13-acetate) to undergo megakaryocytic (MK) differentiation and has been used as a cell model for studying MK differentiation. The Rho family belongs to the small GTPase superfamily and GDP-dissociation inhibitor α (RhoGDIα) suppresses the activity of Rho. Our previous study has shown that RhoGDIα promoted MK differentiation. RhoGDIα has been reported to contain three di-methylated arginines (R111, R152 and R180) however their function is not reported. In addition, our previous results also showed that protein arginine methyltransferase 6 (PRMT6) played a positive role in MK differentiation. This study thus aimed to investigate the functional role of arginine methylation of RhoGDIα and whether PRMT6 mediates methylation of RhoGDIα. In this study, the arginine residues (R111, R152 and R180) were mutated to lysines to mimic the non-methylated state. By ectopic expression, my results showed that single, double and triple mutations lost, to different extent, their stimulatory effects on MK differentiation of K562 cells. Besides R180K, all the mutants appeared to have a dominant negative effect. In the RhoGDIα knockdown (KD) cells, R111K and R152K single mutants still promoted MK differentiation however to a lower degree than wild type did. R111/152K and R111/152/180K double mutants completely lost their stimulatory effects. R111/180K and R152/180K had a similar effect to R111K and R152K single mutants. Together, these results suggest methylation on R111 and R152 plays a more significant role than R180 in promoting MK differentiation. Overexpression of PRMT6 in RhoGDIα KD cells could no longer promoted MK differentiation. When co-expressed with RhoGDIα, PRMT6 regains its ability to promote differentiation in RhoGDIa knockdown cell; while co-expression with RhoGDIα R111/152K did not help regaining the ability. Notably, PRMT6 methylated RhoGDIα in in vitro methylation. These results suggest that PRMT6 may be responsible for methylation of R111 and R152 of RhoGDIα which then promote PMA-induced megakaryocytic differentiation of K562 cells. This study provides links suggesting a positive role of RhoGDIα arginine methylation in MK differentiation.
Gulbrandsen, Ann Cecilie, i Thor Martin Svartaas. "INFLUENCE OF A SYNERGIST ON THE DISSOCIATION OF HYDRATES FORMED IN THE PRESENCE OF THE KINETIC INHIBITOR POLY VINYL CAPROLACTAM". 2008. http://hdl.handle.net/2429/1070.
Pełny tekst źródłaLin, Wen-Ling, i 林玟伶. "To investigate the potential role of Rho GDP dissociation inhibitor α (RhoGDIα) in PMA-induced megakaryocytic differentiation of K562 cells". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/e8svf9.
Pełny tekst źródła國立陽明大學
生物藥學研究所
99
The mitogen-activated protein kinase (MAPK) pathways regulate various cellular functions, including differentiation. Activation of Erk MAPK pathway promotes megakaryocytic (MK) differentiation and p38 MAPK pathway plays a negative role in MK differentiation. K562 is a multipotent human leukemia cell line which can be induced to differentiate into various lineages including megakaryocytes. Upon PMA (phorbol 12-myristate 13-acetate) treatment, K562 cells display characteristics of MK and are often used as a model cell line. Our previous study demonstrated that PRMT1 (protein arginine methyltransferase 1) inhibited PMA-induced MK differentiation of K562 cells via activation of p38? MAPK. However, the molecular mechanism is unclear. The activity of the p38 MAPK pathway is regulated by the upstream MAPKK and MAPKKK and small G proteins such as Rho family. The Rho GDP-dissociation factor ? (RhoGDI?? is known to inhibit activity of Rho GTPases and has been shown to contain three arginine residues that can be dimethylated. This study showed that RhoGDI? plays a positive role in PMA-induced MK differentiation of K562 cells as demonstrated by changes in cytological characteristics. Activation of p38 was enhanced in RhoGDI? knockdown cells by Western blot analysis. Suppression of MK differentiation in RhoGDI? knockdown cells was reverted upon treatment of p38 inhibitor (SB203580). RhoGDI? could reverse the MK differentiation in p38β knockdown cells but not in p38? knockdown cells. In context with PRMT1, promotion of MK differentiation by RhoGDI? was reversed. Mutations at Arg111 or Arg152, which are known to be methylated in cells, abolished the promotion of MK differentiation by RhoGDI?? Together, our results suggest, for the first time, that RhoGDI? and the potential role of methylation regulates PMA-induced megakaryocytic differentiation of K562.
Kawamura, Taro, Michika Ohtake, Yasuhide Sakamoto, Yoshitaka Yamamota, Hironori Haneda, Takeshi Komai i Satoru Higuchi. "EXPERIMENTAL STUDY OF ENHANCED GAS RECOVERY FROM GAS HYDRATE BEARING SEDIMENTS BY INHIBITOR AND STEAM INJECTION METHODS". 2008. http://hdl.handle.net/2429/1401.
Pełny tekst źródłaKwasek, Anna. "Kinetyczne i termodynamiczne badania oddziaływań hemu z ludzką $\alpha_{1}$-mikroglobuliną". Praca doktorska, 2011. https://ruj.uj.edu.pl/xmlui/handle/item/274859.
Pełny tekst źródłaBoyle, David. "Surface Complexation Modelling of the Adsorption of Cd(II), Cu(II), and Ni(II) to the Roots of Triticum turgidum". Thesis, 2012. http://hdl.handle.net/10214/5315.
Pełny tekst źródłaNatural Sciences and Engineering Research Council of Canada, The Mining Association of Canada, Ontario Power Generation, Environment Canada.
Raina, Anupam. "Neurodegeneration induced by ß-synuclein in the context of the neurotransmitter dopamine". Doctoral thesis, 2019. http://hdl.handle.net/00-1735-0000-0003-C011-0.
Pełny tekst źródłaLorinčíková, Kateřina. "Stanovení a porovnání elektromigračních vlastností markerů pro izoelektrickou fokusaci". Master's thesis, 2021. http://www.nusl.cz/ntk/nusl-448696.
Pełny tekst źródłaTummanapelli, Anil Kumar. "Ab Initio Molecular Dynamics Studies of Bronsted Acid-Base Chemistry in Aqueous Solutions". Thesis, 2015. http://etd.iisc.ernet.in/2005/3943.
Pełny tekst źródła