|
|
Study of the role of the B-chain N-terminus conformation of insulin in binding to the insulin receptor
Kosinová, Lucie ; Žáková, Lenka (advisor) ; Obšil, Tomáš (referee)
According to the International Diabetes Federation (IDF), there were 371 million people in the age from 20 to 79 years worldwide affected by diabetes in 2012. This means diabetes has become a global epidemic disease and, therefore, the importace of insulin research still grows. Insulin is a protein hormone that plays a key role in regulating blood glucose level which has a widespread impact on whole metabolism. Insulin acts through binding of its monomeric form to the insulin receptor. It is clear that insulin monomer has to undergo structural changes upon binding to the insulin receptor as the residues which are crucial for the interaction are burried within the native form. According to studies of highly active hormone analogs and the new information about the insulin-insulin receptor complex, there is a strong evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Probably, there is also a great importance of the B-chain N- terminus and the transition between T and R conformations of insulin. However, the exact significance of the T and R states of insulin still remains unclear. In this work, several new insulin analogs AibB3-insulin, AibB5-insulin, AibB8- insulin, N-MeAlaB8-insulin and D-ProB8-insulin were prepared for the purpose of...
|
|
|
Development of an alternative synthesis of Sm-pdta, a chiral NMR shift reagent for amino acids analysis
Hrubá, Lucie ; Vaněk, Václav (advisor) ; Pohl, Radek (referee)
This bachelor thesis deals with the preparation of chiral shift reagents sodium [(R)- and (S)-1,2-diaminopropane-N,N,N',N'-tetraacetate]samarate, for short Sm-(R)-pdta and Sm-(S)-pdta. These reagents have the ability to differentiate NMR signals of enantiomers of amino acids in an aqueous environment. The main aim of this work was to develop a new, efficient and cheap method of the preparation of these reagents which would enable their routine use in laboratory practice, because these reagents are commercially available only in limited quantities and at high price. This work describes simplifield method of separation of racemic 1,2-diaminopropane to its enantiomers from easily available starting substances, L-tartaric acid and racemic 1,2-diaminopropane. We also developed and optimized a new process of synthesis of the key intermediate, (R)- and (S)-1,2-diaminopropane-N,N,N',N'-tetraacetic acid from (R)- and (S)-1,2-diaminopropane dihydrochloride, with a new synthetic step involving tetrabenzylester of this acid and its deprotection by hydrogenolysis without contamination by extraneous ions. This process affords very pure anhydrous acid in high yield. Finally, the target complexes Sm-(R)-pdta and Sm-(S)-pdta were successfully prepared from (R)- and (S)-1,2-diaminopropane-N,N,N',N'-tetraacetic acid...
|
|
|
Synthesis and characterization of ABA triblock copolymers modified with glucose via thiol - ene click reaction
Hašpl, Adam ; Uchman, Mariusz Marcin (advisor) ; Štěpánek, Miroslav (referee)
The bachelor thesis is focused on method of postpolymerisation modification of two poly(ethylene oxid-b-1,2-butadiene-b-ethylene oxide) amphiphilic block copolymer samples with high content of 1,2-isomer units in inner polybutadiene block by thiolene click. The implemented modification agent was 1-thio-β-D-glucose tetraacetate. The thesis is further focused on methods of copolymer sample characterization before and after modification reaction. Structure and degree of functionalization of vinylic units in polybutadiene block after modification was determined by nuclear magnetic resonance spectroscopy. The dimensions of prepared polymeric particles were studied by static and dynamic light scattering methods. Keywords: ABA triblock copolymers, self-assembly, click reaction, NMR spectroscopy, light scattering
|
|
|
SYNTHESIS AND CHARACTERIZATION OF NANOMATERIALS CONTAINING BORON COMPOUNDS
Vrbata, David ; Uchman, Mariusz Marcin (advisor) ; Hrubý, Martin (referee) ; Sedláková, Zdeňka (referee)
This thesis is focused on synthesis and polymerization of caprolactone and its derivatives by living ring opening polymerization (LROP), Self-assembly in aqueous solutions produced nanoaggregates comprised of amphiphilic block copolymers or telechelic polymers with incorporated boron compounds (phenyl boronic acids and boron clusters). Incorporation of boron compounds was facilitated either by covalent or non-covalent bonding. Obtained complex nanoparticle structures manifested stimuli-responsive behaviour and were investigated under varying conditions by combination of light scattering, fluorescence spectroscopy and electron microscopy. The obtained results on solution behaviour of polymers in combination with added value of boron compounds, yield general aspects of nano aggregate morphology, responsive character tuning and practical aspects of synthesis and self-assembly overcame in the preparation process. The publications wrote during this thesis are therefore adding valuable information to researchers engaged in biomedical utilization of such nano assemblies.
|
|
|
N-oxides of morphinan alkaloids
Palušák, Martin ; Dračínská, Helena (advisor) ; Chmelík, Josef (referee)
Morphinan alkaloids belong to important class of compounds acting as painkillers. Understanding of the mechanism of their action is important for improved therapy using these alkaloids, for example, through the synthesis of new analogues with improved effect. The goal of this work is to summarize existing knowledge of these compounds including information about their biosynthesis in the plants and overall effect on the organism. The goal of the practical part of the work is a determination of the relative configuration of morphinan N-oxides produced by in situ oxidation of parent alkaloids using NMR spectroscopy and molecular modelling. Relative configurations of both oxidized and non-oxidized forms of morphine, codeine and thebaine were analyzed using NMR spectroscopy. NMR spectra were analyzed to detect ratio of different N-oxide products in situ. These values were compared with results of DFT quantum chemical computation. Using correlation analysis, reliability of computational method was verified. (in Czech) Key words: NMR spectroscopy, morphine, codeine, thebaine, N-oxides, metabolism of alkaloids
|
|
|
Acid-base equilibria and tautomerism of nucleobases
Kovács, Jakub ; Dračínská, Helena (advisor) ; Petrželová, Simona (referee)
Nucleic acids and their components belong to the most important molecules essential for life. Hydrogen atom migration across the skeleton of purine or pyrimidine bases of nucleic acids gives rise to their various tautomeric forms. Furthermore, depending on pH of the medium, these bases might become protonated or deprotonated. Protonation/deprotonation of nucleic acid bases is involved in many biochemical processes. These include mainly regulation of replication and gene expression by means of specific secondary structure stabilization or acid- base catalysis of phosphodiester backbone cleavage. Additionally, secondary structures that include ionized bases are also associated with various genetic diseases. However, protonation and deprotonation are very fast dynamic processes and their experimental detection is difficult. Therefore, this work focuses on development of reliable method for relatively fast detection of pyrimidine base derivates primary protonation site. At first, pyrimidine bases with protonation site determined by structure were analyzed in both neutral and ionized state using NMR spectroscopy. In the next step, NMR parameters for both neutral and ionized forms were calculated using quantum-chemical computational methods. Computational method was optimized to produce results which...
|
|
|
Antimicrobial peptides isolated from the venom of hymenopterous insect
Monincová, Lenka ; Čeřovský, Václav (advisor) ; Macek, Tomáš (referee) ; Fusek, Martin (referee)
Rapid development of bacterial resistance and multiresitance to conventional antibiotics has resulted in an intensive search for alternative antimicrobial agents. Antimicrobial peptides (AMPs) belong to promising anti-infective candidates since they do not development bacterial resistance. They kill microbes by disturbing or permeabilizing the cytoplasmic membrane, or may target putative key intracellular compartments. Their advantages include fast action and selectivity between prokaryotic and eukaryotic cells. We have isolated several novel AMPs from the venom of wild bees: halictines (HAL-1 and HAL-2) from Halictus sexcinctus, lasiocepsin (Las) from Lasioglossum laticeps and macropin (MAC-1) from Macropis fulvipes. They are active against Gram-positive and Gram- negative bacteria and against yeast Candida albicans. While halictines and macropin have moderate hemolytic activity, Las shows no hemolytic activity. A novel AMP was isolated also from the mucus of Xiphydria camelus. This AMP belongs to the category of insect defensins. It contains 55 amino acid residues, three disulphide bridges and its C-terminus is amidated. CD and NMR studies of HAL-1, HAL-2 and MAC-1 revealed propensity to form amphipathic α-helical structure in the presence of sodium dodecyl sulfate or trifluoroethanol. For the...
|
|
|
Support material for teaching NMR spectroscopy at secondary schools
Tomanová, Marie ; Tošner, Zdeněk (advisor) ; Hrubý, Martin (referee)
Nuclear magnetic resonance is an important, irreplaceable and very common method used in chemistry and medicine. From this perspective, it is highly desirable to implement NMR spectroscopy into high school education. But unfortunately there is not enough material in the Czech language, which would correspond to a high school student's level of knowledge. This thesis looks at creating support materials for teaching NMR spectroscopy and the possibilities of its implementation into high school education. For this purpose, following materials were prepared: an educational text, tests and a database of measured spectra (appendix on CD). Materials were tested in the form of a directed interview and then modified according to the results. This testing confirmed that the text is clear, motivating, and that this topic would be appreciated by both students and teachers. The materials will be available for teachers and high school students at the educational portal studiumchemie.cz. Powered by TCPDF (www.tcpdf.org)
|
|
|
Study of the role of the B-chain N-terminus conformation of insulin in binding to the insulin receptor
Kosinová, Lucie ; Žáková, Lenka (advisor) ; Obšil, Tomáš (referee)
According to the International Diabetes Federation (IDF), there were 371 million people in the age from 20 to 79 years worldwide affected by diabetes in 2012. This means diabetes has become a global epidemic disease and, therefore, the importace of insulin research still grows. Insulin is a protein hormone that plays a key role in regulating blood glucose level which has a widespread impact on whole metabolism. Insulin acts through binding of its monomeric form to the insulin receptor. It is clear that insulin monomer has to undergo structural changes upon binding to the insulin receptor as the residues which are crucial for the interaction are burried within the native form. According to studies of highly active hormone analogs and the new information about the insulin-insulin receptor complex, there is a strong evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Probably, there is also a great importance of the B-chain N- terminus and the transition between T and R conformations of insulin. However, the exact significance of the T and R states of insulin still remains unclear. In this work, several new insulin analogs AibB3-insulin, AibB5-insulin, AibB8- insulin, N-MeAlaB8-insulin and D-ProB8-insulin were prepared for the purpose of...
|
|
|
Organophosphorus derivatives for "click-chemistry"
Zemek, Ondřej ; Kotek, Jan (advisor) ; Veselý, Jan (referee)
Ondřej Zemek Organophosphorus derivatives for "click-chemistry" In this diploma thesis two new macrocyclic ligands were synthesized. They have DO3A moiety where metal (lanthanide) ion can be coordinated and terminal acetylenic or azide group connected through the phosphinic acid. Both terminal acetylenic and azide group should serve for connecting to another molecules or partitions by mean of "click chemistry" i.e. [1,3] copperI catalyzed dipolar cycloaddition between azide and acetylene. In this thesis two ligands, its complexes with some lanthanides as well as its precursors were prepared and characterized. Gd3+ complexes will be further used and studied for potential MRI contrast agents applications.
|
guest ::
