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New method of peptide separation using electrostatic binding
Palágyi, Attila ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
The diploma thesis deals with the development of a new method of synthetic peptide separation using electrostatic binding. It deals with the development of a multi-charged anchored linker attachable to a synthetic peptide after its synthesis on solid phase. Subsequently, it investigates the separation using electrostatic binding; however, after peptide cleavage from the anchored linker and Boc deprotection with TFA, the peptide formed so strong electrostatic interactions with the cation exchanger that we were unable to recover it. The thesis is finished with discussion and method improvement proposal. Key words: peptide separation, solid-phase peptide synthesis, SPPS, electrostatic binding
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Synthesis of 9-deazaguanine derivatives as potential inhibitors of tRNA-guanine transglycosylase (TGT)
Chylíková, Barbora ; Hocek, Michal (advisor) ; Smrček, Stanislav (referee)
Shigellosis is an acute diarrheal disease caused by enterobacteria of the genus Shigella. Worldwide, these bacteria are responsible for about 1 million deaths out of 165 million cases of the disease yearly, of which children under the age of 5 from developing countries are the most vulnerable group. The enzyme tRNA-guanine transglycolase (TGT for short) has been identified as essential for the effective pathogenesis of Shigella bacteria and therefore becomes a potential target for the selective treatment of shigellosis. This bachelor thesis describes the optimization of the preparation of a key intermediate for the synthesis of potential TGT inhibitors based on 8-aryl-9-deazaguanine structure. The synthesis starts from commercially available 2,6-dichloro-9-deazapurine. The main steps of the synthesis are the hydrolysis at position 6, the nucleophilic aromatic substitution of the chlorine group for the amino group in position 2, further the iodation and the introduction of the 3-thienyl group in position 8 by Suzuki coupling.
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Acyclic nucleosides of 3-hydroxypyrazine-2-carboxamide bases
Chaloupecká, Ema ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
This thesis deals with the preparation of acyclic nucleosides and nucleoside phosphonates of compounds T-705 (6-fluoro-3-hydroxypyrazine-2-carboxamide) and T-1105 (3-hydroxypyrazine-2-carboxamide). Acyclic nucleoside phosphonates are substances that can terminate viral RNA or DNA replication, and some of them are used in the treatment of viral diseases. T-705 and T-1105 have shown activity against the influenza virus, and T-705 has already been approved for its treatment in Japan. Since both compounds mimic natural nucleobases in the body, their acyclic nucleosides and nucleoside phosphonates also have the potential to be biologically active. Methods for the synthesis of 3-fluoro-2-(phosphonomethoxy)propyl and 3-hydroxy-2-(phosphonomethoxy)propyl derivatives of T-705 and T-1105, their prodrugs containing lipophilic groups for the improvement of the pharmacokinetic properties and also their phosphonate diphosphates, suitable for the biological activity measurements, have been proposed. Some of these derivatives were subsequently prepared. Key words: acyclic nucleosides, acyclic nucleoside phosphonates, T-705, T-1105, favipiravir, antiviral activity, influenza
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Interaction of selected cosmetic additives with biotransformation enzymes
Bušovská, Radka ; Hodek, Petr (advisor) ; Smrček, Stanislav (referee)
Substances which cause an endocrine dysfunction have a negative impact on the human body and can be found all around us. One of the main mechanisms of their action is the binding to cell receptors or the inhibition of key enzymes involved in steroid hormone synthesis. In this study, the inhibitory effect of selected perfumes and car air fresheners on the activity of aromatase, the key enzyme of steroidogenesis, was examined. Aromatase converts male sex hormones into the female ones. Inhibition of this enzyme results in decreased estrogen concentrations and may thus affects human fertility. The aromatase activity was examined based on the aromatization reaction of testosterone into estradiol. The formation of estradiol was monitored by TLC method. Based on the results of the pilot study the tested perfumes do not significantly inhibit the aromatase activity, while air fresheners in cars appear to be potential aromatase inhibitors. Keywords: Endocrine dysfunction, steroidogenesis, aromatase, perfumes, air fresheners, TLC, chromatography
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Interaction of selected cosmetic additives with biotransformation enzymes
Bušovská, Radka ; Hodek, Petr (advisor) ; Smrček, Stanislav (referee)
Endocrine disruptors are nowadays very often discussed, due to their negative impact on the human body. They can be found all around us and they've become a parf of our everyday life, even if many people don't even realize it. Cosmetic products and perfumes are part of everyday life and just few of many people realize the consequences of having regular contact with our skin. Perfumes and fragrances are part of all cosmetic products or various commonly used industrial products, that people could not even live without. Perfumes can have a negative effect on the health of the organism and, due to the large number of chemicals they consist of and the interactions with each other and the subsequent interaction with important enzymes such as aromatase, they can belong to the group of hormone-active substances. The aim of this work was to find out by TLC (Thin Layer Chromatography) analytical method whether various perfumes and industrial car smells can disturb the endocrine system by inhibiting the key enzyme, aromatase. Experiments have shown that the commonly used fragrances really interact with aromatase. Keywords: Endocrine disruptors, aromatase, TLC, chromatography, perfumes, industrial fragrances
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Phytoextraction of Benzodiazepines from Water Solutions
Grasserová, Alena ; Smrček, Stanislav (advisor) ; Soudek, Petr (referee)
Abstract, key words The aim of this thesis was to perform a phytoextraction experiment with benzodiazepines chlordiazepoxide, diazepam, alprazolam and bromazepam on corn plant (Zea mays). After 14 days of growing of sterile cultivation, new medium (Murashige and Skoog) contaminated with benzodiazepine was added. The starting concentration of benzodiazepine was 10 mg · l-1. After every 24 hours, a sample of medium was collected. The actual concentration of benzodiazepine was measured on HPLC with UV detection. Extractable residues were also analysed to find out whether the benzodiazepine is being translocated to the upper parts of the plant. The same HPLC conditions were used for these samples. The greatest phytoextraction efficiency (the amount of drug extracted by 1 gram of biomass in 24 hours) was observed for chlordiazepoxide, followed by bromazepam, alprazolam and diazepam respectively. The extractable residues analysis confirmed the translocation to the upper parts of the plant for every of the benzodiazepines tested. That indicates a threat for the animals through the food chain contamination. Key words: phytoremediation, phytoextraction, benzodiazepines, extractable residuals, HPLC.
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Biosynthesis of the bumblebee male pheromones and its hormonal regulation.
Bártová, Adéla ; Valterová, Irena (advisor) ; Smrček, Stanislav (referee)
Bumblebees are important pollinators, commercially used in large-scale plant growing in greenhouses. Their males produce marking pheromones for mating, which attract young bumblebee queens. These pheromones are often a complicated mixture of chemicals, which is produced in the male labial gland, and the mixture itself is specific for each bumblebee species. The regulation of bumblebee sexual pheromone biosynthesis is largely unknown, and this Master's thesis is focused on the analysis of the mechanisms which lead to the regulation of the Bombus terrestris male pheromone's fat-acid and terpenes biosynthesis, specifically on stereospecific enzymatic reduction of double bond of farnesol. This thesis studies the influence of potential neurohormones on a specific enzymatic mixture, which is involved in the pheromone biosynthesis. Methods used in this project include biochemical, analytic and molecular-biology methods.
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