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Evaluation of Rate Constants from Protein-Ligand Interactions with Weak Affinity ChromatographyJönsson, Daniel January 2012 (has links)
The paradigm of drug discovery have been to find the strongest possible binder to the target by high-throughput screening (HTS) but high affinity interactions are related to low kinetic off rates and thus result in severe side-effects and non-approved drugs. Lead molecules working in a transient manner (KD > µM) will allow for rapid off rates and possibly less side-effects. In this study the peak profile method applied to weak affinity chromatography (WAC) was evaluated as a simple way to provide the kinetics of the interaction and thereby allowing for high-throughput determinations. In the peak profile formula all band-broadening effects except the stationary mass transfer is subtracted which simplifies the calculations for the kinetics of the interaction tremendously. The technique was evaluated by screening of 3 different benzamidines at 3 linear flow-rates using zonal chromatography and human α-thrombin as immobilized target protein. The kinetics of the interaction could unfortunately not be determined. This was possibly due to the flow-rates not being high enough as indicated by a low critical ratio (η < 1). Higher flow-rates would increase the contribution to band-broadening due to kinetic effects but would also require more precise estimation of peak variance.
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Colunas empacotadas em cromatografia líquida capilar: desenvolvimento de hardwares e avaliação de suas contribuições no desempenho cromatográfico / Packed columns for capillary liquid chromatography: hardware development and evaluation of its contribution to the chromatography performanceBorsatto, João Victor Basolli 27 July 2018 (has links)
Essa dissertação de mestrado descreve o desenvolvimento de hardwares de colunas para cromatografia líquida capilar. O processo de desenvolvimentos desses dispositivos é descrito gradativamente e os pontos fortes e as limitações de cada modelo de hardware são discutidos. O melhor modelo de hardware desenvolvido apresentou produção simples, fácil conexão ao sistema cromatográfico e resistência a pressões superiores a 900 bar. Sucessivamente ao estabelecimento de um modelo de hardware apropriado, os efeitos dos materiais do hardware na eficiência das colunas foram avaliados. Poucos estudos relatam a influência do hardware nas separações em escala capilar, de forma que essa dissertação contribui para o preenchimento dessa lacuna. Capilares de aço inoxidável e sílica fundida e frits de aço inoxidável e fibra de vidro foram avaliados. Colunas com eficiências superiores a 100.000 pratos por metro foram produzidas. / This master\'s dissertation describes the development of hardware for capillary liquid chromatography columns. The development process of the devices is described gradually and the strengths and limitations of each model of hardware are discussed. The best-developed hardware model presented easy production, practice connection to the chromatographic system and resistance to pressures greater than 900 bar. After the establishment of an appropriate hardware model, the effects of hardware materials on the efficiency of the columns were evaluated. Few studies report the influence of the hardware on capillary scale separations; therefore, this dissertation contributes to fill this gap. Capillaries of stainless steel and fused silica and frits of stainless steel and glass fiber were evaluated. Columns with efficiencies greater than 100,000 plates per meter were produced.
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Colunas empacotadas em cromatografia líquida capilar: desenvolvimento de hardwares e avaliação de suas contribuições no desempenho cromatográfico / Packed columns for capillary liquid chromatography: hardware development and evaluation of its contribution to the chromatography performanceJoão Victor Basolli Borsatto 27 July 2018 (has links)
Essa dissertação de mestrado descreve o desenvolvimento de hardwares de colunas para cromatografia líquida capilar. O processo de desenvolvimentos desses dispositivos é descrito gradativamente e os pontos fortes e as limitações de cada modelo de hardware são discutidos. O melhor modelo de hardware desenvolvido apresentou produção simples, fácil conexão ao sistema cromatográfico e resistência a pressões superiores a 900 bar. Sucessivamente ao estabelecimento de um modelo de hardware apropriado, os efeitos dos materiais do hardware na eficiência das colunas foram avaliados. Poucos estudos relatam a influência do hardware nas separações em escala capilar, de forma que essa dissertação contribui para o preenchimento dessa lacuna. Capilares de aço inoxidável e sílica fundida e frits de aço inoxidável e fibra de vidro foram avaliados. Colunas com eficiências superiores a 100.000 pratos por metro foram produzidas. / This master\'s dissertation describes the development of hardware for capillary liquid chromatography columns. The development process of the devices is described gradually and the strengths and limitations of each model of hardware are discussed. The best-developed hardware model presented easy production, practice connection to the chromatographic system and resistance to pressures greater than 900 bar. After the establishment of an appropriate hardware model, the effects of hardware materials on the efficiency of the columns were evaluated. Few studies report the influence of the hardware on capillary scale separations; therefore, this dissertation contributes to fill this gap. Capillaries of stainless steel and fused silica and frits of stainless steel and glass fiber were evaluated. Columns with efficiencies greater than 100,000 plates per meter were produced.
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Advances in chain-growth control and analysis of polymer: boosting iodine-mediated polymerizations and mastering band-broadening effects in size-exclusion chromatographyWolpers, Arne 10 November 2014 (has links)
No description available.
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