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Carbocyclic analogues of nucleosides containing substituted bicyclic systems.
Šála, Michal ; Hřebabecký, Hubert (advisor) ; Černý, Miloslav (referee) ; Moravcová, Jitka (referee)
Charles University in Prague Faculty of Science Department of Organic and Nuclear Chemistry Carbocyclic analogues of nucleosides containing substituted bicyclic systems Michal Šála Ph.D. Thesis Abstract Prague 2010 Introduction Nucleoside and nucleotide analogues are of fundamental importance for all organisms. Therefore, nucleoside analogues are interesting target for drug discovery and development, mainly as potential antiviral and antitumor agents. A crucial disadvantage of natural nucleosides analogues is cleavage of the N-glycosidic bond by phosphorylases. Modification which increases resistance against enzymatic degradation is substitution of the sugar moiety furanose ring by a hydrocarbon ring. Many of such modified analogues - carbocyclic nucleosides1 - exhibit interesting antiviral activity. Several analogues containing conformationally locked bicyclic systems were also synthesized. Well known are carbocylic nucleosides with a fused cyclopropane moiety2 (bicyclo[3.1.0]hexane). Recently, novel conformationally locked carbocyclic nucleosides based on 2-oxabicyclo[2.2.1]heptane ring system were described3 (as precursors for carbocyclic locked nucleic acids). This thesis concerns the synthesis of biologically active compounds related to the carbocyclic nucleoside analogues. First part of the work is...
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Virtual worlds - construction of the past as a game. Amateur historical fencing
Moravcová, Jana ; Štěpánová, Irena (advisor) ; Kašpar, Oldřich (referee)
This diploma thesis concerns on one way of leisure time spending in Czech Republic - non-professional historical fencing. This activity lays essentially in depicting of battle manners in the past in fonn of dramatic performances (public presentation is not required though). The actors use for their purposes armament, outfit, clothing and other equipment that should correspond at least generally to a certain historical period. In the first part of the work I set historical fencing into broader context of leisure time activities with common features, which are RPG's (Role Playing Games) and LARP's (Live Action Role Playing) and leisure time activities with fantasy thematics generally on one side, and other ways of depicting of the past, mainly historical music, historical dance and "living history" on the other. In the next part I try to explain current meaning of the term "historical fencing" and to briefly survey evolution of historical fencing in our country from the 60's until today. I watch non-professional historical fencing actors themselves more closely, explore their associating into groups, fonnal structure of such associations (groups) and cite examples of several Prague based groups. I also deal with motivation of actors for historical fencing, non-concerned public's view of such activity and...
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Annotated translation: Architektur ist nämlich ganz einfach. Selected chapters.
Moravcová, Jana ; Kloudová, Věra (advisor) ; Žárská, Monika (referee)
This bachelor thesis consists of translations of selected chapters from the book 'Architektur ist nämlich ganz einfach' and a commentary. The book was written by Christiane Tramitz and Wolfgang Bachmann. It contains adapted interviews with 33 architects, who come from German speaking countries. My aim has been to create a functionally equivalent translation with a precise commentary. The commentary consists of a translation analysis of the source text based on the model of Christiane Nord. Following the translation analysis, I comment on the typology and my solutions to translation problems I came across. Finally, I describe translation shifts which occurred during the translation process, while referring to Jiří Levý's and Anton Popovič's theories.
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Proposal of the Motivation System in the Company
Vejnarová, Michaela ; Moravcová, Jana (referee) ; Novák, Petr (advisor)
This diploma thesis focuses on the analysis and improvement of company Zebra Technologies CZ s.r.o. First part of thesis is devoted to theoretical concepts related to this topic. In second analytical part, the company is introduced, analysis of motivation program and evaluation program of the company is carried out. Last part is focused on proposed measures to improve the company’s motivation system based on the results from analysis part of thesis.
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Modified Substrates in β-N-Acetylhexosaminidase-Catalyzed Synthesis
Bojarová, Pavla ; Křen, Vladimír (advisor) ; Moravcová, Jitka (referee) ; Walterová, Daniela (referee)
4 Conclrrsion 4 CoNcrusroN This Ph. D. thesis is a systematic study of the substrate specificity and the synthetic potential of B-N-acetylhexosaminidases (EC 3.2.1.52) with structurally modified substrates. It comprises four publications in intemational journals, one review and 17 oral and poster contributions. The following parts of the substrate molecule were modified: 2-acetamido moiety, the C-6 hydroxyl (oxidations, introduction of a cyano group) and the aglycon part (glycosyl azides - C-N bond hydrolysis). Thirteen modified substrates were synthesized, seven of them were described for the first time. They were tested for hydrolysis and transglycosylation by over thirty fungal $-N-acetylhexosaminidases (culture collections at Charles University and at the Institute of Microbiology, Academy of Sciences of the Czech Republic) and the results were discussed in relation to the conclusions of molecular modeling (B-N-acetylhexosaminidase from Aspergillus oryzae CCF 1066). Eight oligosaccharidic structures (six of them novel) were prepared by semi- preparative transglycosylation reactions (tens of miligrams), isolated (mostly 16_377a yields, even 787o yie\ď) and fully characterized. Noteworthy properties like immunoactivity (binding to natural killer cell activation receptors) and inhibitory potential were...
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Transition metal complexes catalyzed synthesis of biologically active estrone derivatives
Prchalová, Eva ; Kotora, Martin (advisor) ; Moravcová, Jitka (referee) ; Hlaváč, Jan (referee)
This thesis relates to the preparation and use of new non-estrogenic ligands selective for certain types of the 17β-hydroxysteroid dehydrogenase superfamily (17βHSD). Such nonestrogenic compounds, which selectively regulate the activity of 17βHSD are believed to offer new solutions in endocrine therapy, diagnosis and treatment of estrogen-dependent types of diseases. In recent years in the laboratories of my supervisor prof. Kotora differently substituted steroid derivatives with interesting biological properties were prepared. Based on the gained experiences, it was decided to prepare C-15 estrone derivatives. Such compounds are mostly unexplored, and therefore they might be a new class of interesting biologically active compounds. A method was developed for the preparation of C-15 estrone derivatives. Estrone, the starting material for the synthesis, was first converted to the appropriate intermediate, protected estra-1,3,5(10),15-tetraene-17-one. Conjugate addition of vinylmagnesium bromide to this enone yielded the starting material for further reactions, 15β-vinylestrone. Cross metathesis of 15β-vinylestrone with suitable terminal olefins provided large series of C-15 estrone derivatives with perfluoroalkylated, aliphatic and aromatic side chains. Selected unsaturated derivatives were tested...
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Synthesis of biologically active compounds with quinazoline scaffold
Štěpánek, Ondřej ; Kotora, Martin (advisor) ; Hájíček, Josef (referee) ; Moravcová, Jitka (referee)
This thesis concludes my contribution to research of HIV-1 capsid assembly inhibitors. It has been shown that 2,4-disubstituted quinazoline derivatives are able to inhibit this process both, in competitive biochemical assay based on the AlphaScreen technology as well as in tissue cultures. The main objective of the work was to prepare the aforementioned quinazolines, to design and prepare new candidates with higher activity based on results of biochemical tests, and also to try to increase the solubility of otherwise poorly soluble compounds. Disubstituted quinazolines are relatively easily accessible from the commercially available anthranilic acid derivatives. These are converted to the corresponding quinazolin- 4(3H)-ones by the condensation reactions. In this work, two methods were used for the preparation of quinazolin-4(3H)-ones: reaction of acyl chlorides with aromatic anthranilamides provided 2-arylamidobenzamides whose subsequent cyclisation under basic conditions led to derivatives of 2-arylquinazolin-4(3H)-one; reaction of anthranilic acid esters with aromatic nitriles, which afforded desired quinazolin-4(3H)-one in one reaction step. Chlorination of 2-arylquinazolin-4(3H)-ones using POCl3 then led to 2-aryl-4- chloroderivatives as key intermediates. Nucleophilic substitution of...
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New functionalized nucleic acids for application in chemical biology
Kielkowski, Pavel ; Hocek, Michal (advisor) ; Stiborová, Marie (referee) ; Moravcová, Jitka (referee)
4 Abstract This work is focused on the synthesis of the modified 2'-deoxyribonucleoside triphosphates, their incorporation into DNA and use in chemical biology applications. The synthetic routes to the double-headed nucleosides and nucleotide triphosphates in which the two nucleobases were connected via ethynyl or propargyl linker has been developed. (Cytosin-5-yl)ethynyl, 3-(cytosin-1-yl)prop-1-yn-1-yl and 3-(5-fluorocytosin-1-yl)prop-1-yn- 1-yl derivatives of pyrimidine and 7-deazaadenine 2'-deoxyribonucleosides and nucleoside triphosphates were prepared by aqueous palladium-catalyzed cross-coupling reactions. The double-headed modified nucleoside triphosphates were good substrates for DNA polymerases suitable for primer extension and PCR construction of DNA bearing linked cytosine or 5- fluorocytosine in the major groove mimicking the flliped-out nucleotide. The assay for the testing of the inhibition of DNA methyltransferases was developed. Next, the transient protection of DNA against cleavage by restriction endonucleases (REs) using (trialkylsilyl)ethynyl modified DNA was developed. A series of 7-(trialkylsilyl)ethynyl-7- deaza-2'-deoxyadenosine triphosphates was prepared and they were shown to be incorporated into DNA by primer extension and/or PCR using KOD XL polymerase. The deprotection conditions...
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