|
|
Synthesis and characterization of new insulin derivatives with altered selectivity for insulin and IGF-1 receptors.
Halamová, Tereza ; Jiráček, Jiří (advisor) ; Dračínská, Helena (referee)
Insulin receptor (IR) exists in two isoforms (IR-A and IR-B), which differ in the tissue distribution and probably also in their function, i.e. in their response to insulin binding. It is supposed that IR-A activates mainly mitogenic processes and that IR-B triggers mainly metabolic effects resulting in the uptake of glucose by muscle and fat cells. Insulin can also weakly bind to the receptor for IGF-1 (IGF-1R), a growth factor involved in the regulation of growth and development. Insulin derivatives selectively binding only to one of the receptors would be interesting for the study of the receptors but also potentially for the treatment of diseases such as diabetes or cancer. Here we used our experience in the structure-activity studies of insulin for the design, synthesis and biological characterization of 4 new insulin derivatives in order to modify their selectivity towards the individual receptors. We systematically modified insulin by amidation of the C-terminus of its B-chain or by prolongation of the B-chain by 1-3 carboxyamidated glycine residues. Binding affinities of all new analogues for IR-A and IR-B were determined and for some of the analogues binding affinities for IGF-1R as well. Finally, abilities of analogues to activate autophosphorylation of intracellular subunits of IR-A and...
|
|
|
Experimental study of chemical evolution of biomolecules under early Earth conditions
Knížek, Antonín ; Ferus, Martin (advisor) ; Adam, Vojtěch (referee)
Origin of life is a still-enduring gap in human knowledge. This work is focused on revealing of several pieces of this puzzle. State of the art scenarios of biomolecules synthesis under prebiotic conditions are presented and discussed. This thesis presents our recent experiments suggesting a novel idea that neutral planetary atmosphere containing a mixture of neutral volcanic-type gasses (CO2, N2, H2O) can be converted over acidic mineral catalysts upon irradiation by a soft UV-radiation into a relatively reactive mixture of reducing gases (CH4, CO), which can be further reprocessed by high-energy chemistry. The resulting mixture (CH4, CO + N2) represents a common reducing atmosphere related e.g. to the chemistry of Titan, the largest moon of Saturn, as well as a possible representation of the secondary atmosphere of our planet. Also, photocatalytic reduction of CO2-rich atmosphere can explain the abiotic origin of methane on current Mars or other terrestrial planets. In our subsequent experiments, corresponding equimolar model mixture of CH4 : CO : N2 in presence of water vapour was subjected to reprocessing by high-power laser plasma simulating an asteroid impact - one of a series of impact events which the young Earth experienced during the first 600 million years of her history. Upon delivery...
|
|
|
Synthesis of haemanthamine derivatives
Marková, Jana ; Cahlíková, Lucie (advisor) ; Kuneš, Jiří (referee)
6 Abstract Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Jana Marková Supervisor: doc. Ing. Lucie Cahlíková, Ph.D. Title of Diploma thesis: Synthesis of haemanthamine derivatives Based on previous studies, the haemanthamine alkaloid showing remarkable antitumorous activity was chosen as the subject of this thesis. The purpose of the thesis was preparation of its more active derivatives, namely esters. Preparation concerns the following derivatives: 11- O- butanoylhaemanthamine, 11-O-(3,4-dimethoxybenzoyl)-haemanthamine, 11-O-(4- trifluoromethoxybenzoyl)-haemanthamine, 11-O-isobutanoyhaemanthamine. These were created by the reaction of haemanthamine and the relevant acilating agent (acylchloride, anhydride) in the environment of anhydrous pyridine or tetrahydrofuran with adding dimethylaminopyridine as a catalyst. Most of the products were obtained in the form of colourless oil, one of the substances crystallized into white amorphous crystals. However, during an attempt of dioxolane ring opening, the preparation of 3-demethylhaemanthamine derivative proved unsuccessful. Prepared derivatives were mostly identified by EI-MS and NMR. All the substances were gained in sufficient outcomes in the scale of 43 - 81 %. All the compounds were...
|
|
|
Solution of Continuous Systems by Evolutionary Computational Techniques
Lang, Stanislav ; Šeda, Miloš (referee) ; Olehla, Miroslav (referee) ; Matoušek, Radomil (advisor)
The thesis deals the issue of solution of continuous systems by evolutionary computational techniques. Evolutionary computing techniques fall into the field of softcomputing, an advanced metaheuristics optimization that is becoming more and more a method of solving complicated optimization problems with the gradual increase in computing performance of computers. The solution of continuous systems, or the synthesis of continuous control circuits, is one of the areas where these advanced algorithms find their application. When dealing with continuous systems we will focus on regulatory issues. Evolutionary computing can then become a tool not only for optimization of controller parameters but also to design its structure. Various algorithms (genetic algorithm, differential evolution, etc.) can be used to optimize the parameters of the controller, for the design of the controller structurewe usually encounter so called grammatical evolution. However, the use of grammatical evolution is not necessary if appropriate coding is used, as suggested in the presented thesis. The thesis presents a method of designing the structure and parameters of a general linear controller using the genetic algorithm. A general linear regulator is known also as so called polynomial controller, if we encounter the polynomial theory of control. The method of encoding the description of the general linear controller into the genetic chain is crucial, it determines a set of algorithms that are usable for optimization and influence the efficiency of the calculations. Described coding, effective EVT implementation, including multi-criteria optimization, is a key benefit of this work.
|
|
|
Synthesis and Characterization of Topological crystalline insulators in the SnTe material class
Chovanec, Jakub ; Uhlířová, Klára (advisor) ; Prokleška, Jan (referee)
k bakalářské práci - Anglický jazyk Synthesis and Characterization of Topological crystalline insulators in the SnTe material class Jakub Chovanec July 21, 2017 In this work we prepared series of single crystal samples PbxSn1−xTe and PbxSn1−xSe. These materials are quite popular last few years, after they were predicted and then char- acterized by [4] as topological crystaline insulators (TCI). TCI is a quantum state of crys- tals, in which symetry causes existance of the metal states on the surface. Samples had been prepared from molten flux and by using Bridgman method. Homogenity and pu- rity of single crystals had been determined. Compounds PbxSn1−xTe and PbxSn1−xSe crystalized in cubical structure and were defined as Fm-3m space group, existance of PbxSn1−xSe in Pnma space group were confirmed. 1
|
|
|
Synthesis of supramolecular components with positive charges and study of their binding to plasma treated surfaces
Garbárová, Veronika ; Jindřich, Jindřich (advisor) ; Jelínek, Ivan (referee)
5 Abstract The aim of this work was to synthesize a series of new compounds capable to show supramolecular interactions with cyclodextrins, such as adamantane or ibuprofen, which also contain permanent positive charges. Therefore, they can be bound electrostatically on negatively charged surfaces. Plasma treated surface which contains carboxylate groups and polymer Nafion® 117 with sulfonate groups have been used as such surfaces. The synthesis has started with introduction of the azido group into the molecule and has been followed by copper catalyzed azide/alkyne cycloaddition reaction with a linker containing positive charges and a propargyl group. Optimal conditions of a binding onto the solid surface and a dependence of the bond stability in water solutions on pH and concentration of salts have been evaluated for selected components using UV spectrometry. Key words: synthesis, positively charged compounds, electrostatic binding, plasma treated surfaces
|
|
|
Evolutionary Resynthesis of Combinational Circuits
Kocnová, Jitka ; Sekanina, Lukáš (referee) ; Vašíček, Zdeněk (advisor)
This master thesis is concerned about the resynthesis of combinational circuits with the help of evolutional principles. The first part of this text describes logic synthesis and its weak spots, evolutional synthesis and its advantages, and also some of the existing synthesis programs. The second part shows usage of graph algorithms in logic synthesis and their possible usage in an extension for the chosen synthesis program. Suggested design and practical implementation of the extension is also described in this part. In the third part extension testing is mentioned. The fourth part is the last one and concludes gained knowledge and results.
|
|
| |
|
|
Fluorescently labeled ligands for the Mu-opioid receptors
Hadzima, Martin ; Machara, Aleš (advisor) ; Kohout, Michal (referee)
This Bachelor's thesis deals with preparation of fluorescently labeled opiates, which allow detection of µ-opioid receptors and study of their interaction with ligands, using fluorescent techniques. As substrates designated for chemical modifications were chosen semi-synthetic opiates, naloxone and naltrexone. Their conversion to corresponding C-6 hydrazones allowed further modifications of these substances and tracking, if any changes to their ability to interact with µ-opioid receptors ocurr. Firstly, known adducts of these hydrazones with fluorescein isothiocyanate were prepared. Then, we inserted linkers of different lengths between the opiate fragment and the fluorescent tag, systematically. Mentioned linkers were prepared from tetraethyleneglycole derivatives with aim to study binding constants of modified µ-opioid receptor ligands. In the end, we decided to prepare opiate conjugate with particular linkers of length corresponding, approximately, to decaethyleneglycole. Two different procedures were proposed for the preparation of this linker. One of them used click chemistry concept and the other was based on classic amide coupling. Both conjugates were converted to adducts with fluorescein to verify their specific binding to µ-opioid receptors. They were also provided to co-operating group,...
|
|
|
Preparation of bifunctional organocatalysts
Rohaľová, Dominika ; Veselý, Jan (advisor) ; Trnka, Tomáš (referee)
This bachelor thesis deals with the synthesis of bifunctional thiourea catalysts and corresponding building blocks derived from levoglukosane. The first part was of this thesis is focused on the preparation 1,6:2,3-dianhydro-4-azido-4-deoxy-β-D-mannose. The second part of the thesis is deals with the preparation od bifunctional catalyst. Keywords Asymmetric synthesis, organocatalysis, saccharides, bifunctional calatysts, thiourea, morpholine.
|
guest ::
