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Antioxidative effects of the analogues of nucleic acid components.
Procházková, Eliška ; Mertlíková Kaiserová, Helena (advisor) ; Zusková, Iva (referee)
Reactive oxygen species (ROS) naturally occur in the organisms where they play e.g. signaling and antimicrobial roles. The imbalance between ROS production and removal results in the oxidative stress. This condition is largely considered as unfavourable leading to the oxidative damage of the biomolecules (lipids, proteins, nucleic acids). The oxidative stress accompanies a number of civilization diseases and may also arise as a consequence of pharmacotherapy (side effects of some drugs). Modulation of the oxidative stress with the use of antioxidants remains a subject of intense research. The analogs of nucleic acid components represent a structurally diverse class of compounds with important pharmacological potential. While their antiviral and cytostatic activities have been described in detail, information on their potential antioxidant activity is missing. The aim of this study was to identify the antioxidant activity in a series of 126 analogs of nucleotides, nucleosides and nucleobases and to describe structural motives responsible for this activity. Several methodological approaches have been used to reach the goal: 1) determination of the ability of the compounds to scavenge ABTS radical in vitro (TEAC), 2) the influence of the compounds on lipid peroxidation and 3) their ability to...
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Study of the mechanism of DNA recognition by transcription factor FOXO4
Zusková, Iva ; Obšil, Tomáš (advisor) ; Bouřa, Evžen (referee)
Forkhead transcription factor FOXO4 is involved in a wide range of processes including metabolism control, cell cycle regulation, apoptosis, DNA repair or oxidative stress resistance. The crystal structure of FOXO4 DNA-binding domain bound to the target DNA revealed that FOXO4 interacts with DNA in the same manner as other forkhead proteins. The DNA-binding interface consists of helix H3, which binds to the major groove of DNA, the N- terminal segment and flexible loops located at the C-terminus of forkhead domain. However, many questions concerning the regulation of DNA-binding specificity and the role of different parts of forkhead domain in this process remain elusive. In this diploma thesis, the interactions between the DNA-binding domain of FOXO4 and DNA with various sequences were studied. The DNA-binding domain of FOXO4 and its mutants were expressed and purified and their DNA-binding properties were studied using fluorescence spectroscopy techniques and surface plasmon resonance. Results of these experiments revealed that the nucleotide sequence at the 5′ end of the consensus binding motif affects the stability of the complex between the DNA-binding domain of FOXO4 and DNA. In addition, the importance of individual amino acid residues of FOXO4 that are involved in DNA binding for the...
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Ionic effects and online preconcentration techniques in separation systems
Boublík, Milan ; Zusková, Iva (advisor) ; Tůma, Petr (referee) ; Vigh, Gyula (referee)
Online preconcentration techniques in capillary electrophoresis (CE) improving sensitivity of electrophoretic separations and are in the scope of interest of many research groups. Therefore, proposal of new techniques for preconcentration and their theoretical description is desirable for their wider application. In this thesis, new preconcentration techniques are proposed and models of ionic strength effects in separation systems of CE and hydrophilic liquid interaction chromatography (HILIC) are presented and new set of pI markers for isoelectric focusing (IEF) was showed with their utilization for characterization of IEF pH gradient. Part of this thesis is keen on proposal of new preconcentration techniques and their theoretical description. We presented two preconcentration techniques, while first is based on sweeping with neutral complexing agent, the second one utilizes pH boundaries that are induced by disturbing phenomena of system zones. Both techniques are described theoretically by means of numerical simulations and by experiments. Both techniques are even utilized for real drug sample or for mixture of similar analytes. For system peak preconcentration technique, flow chart of how to design such method is presented. Second part of this thesis have rather more fundamental subject and...
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Complex equilibriums of beta-blockers in CZE
Kanizsová, Lívia ; Zusková, Iva (advisor) ; Jelínek, Ivan (referee)
Drugs used in the pharmaceutical industry often occur as a mixture of several isomers with a different biological activity. In a case that some isomer provides an undesirable side effect, it is important to separate it from the mixture and check the chiral purity of a drug. Capillary zone electrophoresis plays a significant role in chiral separations. A different affinity of isomers to complexation reagent is used for their separation from each other. The extent of their interaction is characterized by the complexation constant. Most commonly the cyclodextrins are used for the chiral separations of β-blockers and they could be in neutral or charged form. They probably interact with them through the creation of inclusion complexes. A successful baseline enantioseparation of all the β-blockers that have been studied, labetalol, pindolol, alprenolol and atenolol, was provided by using the background electrolyte containing charged cyclodextrins. The highest resolution of peaks was observed using sulfated cyclodextrins.
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Determination binding constant of beta-blockers by capillary zone electrophoresis
Kanizsová, Lívia ; Zusková, Iva (advisor) ; Šteflová, Jana (referee)
Capillary zone electrophoresis identifies and determines various analytes based on their mobilities in a solution of the background electrolyte, which is exposed to an effect of the electric field. Besides that, it is a suitable method for determination of dissociation and complexation (stability) constants. In this paper the adrenergic β-blockers were chosen as analytes. β-blockers have at least one chiral center in the structure and separation of their enantiomers in presence of the chiral selectors by capillary electrophoresis is possible. For the enantioseparation, variously modified β-cyclodextrins are most often added to the background electrolyte. If the enantiomers of β-blockers have a different affinity to the chiral selector, they exhibit different effective mobilities. Based on a dependence of the effective mobility of analytes on the concentration of chiral selector, we are able to determine their stability constants. Key words: β-blockers, cyclodextrins, stability constant, capillary zone electrophoresis
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Overview of mathematics for study of physical chemistry
Břížďala, Jan ; Zusková, Iva (advisor) ; Beneš, Martin (referee)
Physical chemistry is a discipline, that is related to the knowledge learned in general chemistry and there is necessary to know some mathematical operations. The bachelor work presents the results of a research, where there was investigated the knowledge of selected mathematical topics among students. Furthermore the level of schooling where the students first learned these topics was being elicited. The outcomes of this survey show that the most difficult mathematical chapters for the students are those, which are essential for physical chemistry. In the following part of the bachelor work some print and e-sources of mathematics are analysed. The crucial part of this work is the summary of mathematical topics essential for the study of physical chemistry. This summary is included in the structure of this bachelor work and it is accesible on-line too. A
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