National Repository of Grey Literature 49 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Synthesis of NIR Reductive Probes to Monitor Hypoxia During Fungal Infection
Kárníková, Tereza ; Baszczyňski, Ondřej (advisor) ; Míšek, Jiří (referee)
Invasive fungal infections represent a significant problem, resulting in approximately 1.5 million deaths worldwide annually. Among the most common invasive fungal infections are aspergillosis and candidiasis. Both opportunistic infections have a high mortality rate (50% and 27%, respectively). The diagnosis of these infections is often complex, leading to delayed detection and an increased risk of complications. Recently, near-infrared (NIR) hypoxia probes have been investigated for the diagnosis and monitoring of fungal infections. These probes enable non-invasive measurement of tissue oxygen concentration and can contribute to early diagnosis of fungal infections. Hypoxia can also be a relevant target for the delivery of antifungal agents. For this reason, a series of hypoxia-selective probes has been developed. These probes contain N-methyl-2-nitroimidazole and a fluorophore that absorbs in the near-infrared spectrum. We anticipate that probes will function as follows: the reducible breakdown of N- methyl-2-nitroimidazole in a hypoxic environment will activate the probe, leading to the release of the fluorophore, which absorbs in the near-infrared spectrum. Confocal microscopy will be used to observe whether the fluorophore is selectively released in the hypoxic environment or at the site of...
Optimization of concentration determination of degrdation products of uracil via LC-MS
Kavale, Gustav ; Ševčík, Jan (advisor) ; Míšek, Jiří (referee)
In the Czech Republic, tens of thousands of oncology patients undergo treatment based on fluoropyrimidines every year. Many of these patients suffer from negative side effects that can even have a fatal impact. Currently, the best described factor in the cause of the toxicity of fluoropyrimidines is the activity of the pyrimidine catabolism enzyme - dihydropyrimidine dehydrogenase. Due to the high frequency of pathogenic mutations in the dihydropyrimidine dehydrogenase gene, the extreme risk of toxicity affects hundreds of patients in the Czech Republic every year. For this reason, the "European Medical Agency" has issued a recommendation to carry out investigations for the possible occurrence of toxic effects before starting treatment. One of the diagnostic options for determining sensitivity to fluorouracil is metabolomic analysis, based on the quantification of degradation products of uracil metabolism in plasma using liquid chromatography with mass spectrometry. The goal of this work is to perform basic optimization of mass spectrometer parameters for quantification of selected degradation products of uracil metabolism. Keywords: Uracil, Fluoruracil, Liquid Chromatography, Mass Spectrometry
Small Molecules as Immune Modulators in Anticancer Therapy
Pavlovová, Anna ; Míšek, Jiří (advisor) ; Smrček, Stanislav (referee)
The aim of this bachelor thesis was to summarize knowledge about several selected therapeutic targets used for cancer immunotherapy and small molecules that can have an immunomodulatory effect on these targets. This is a relatively new and attractive topic in the field of biomedical sciences, which is constantly evolving. Some small molecules have already been approved for treatment of specific cancer diseases, and many more are currently undergoing various stages of clinical trials. This work should provide the reader with an overview of possible approaches to modulate the immune system using small molecules. Key words: small molecules, immunotherapy, cancer, checkpoint inhibitors, tumor microenvironment
Modification of nucleic acids by reactive groups for bioconjugations and cross-linking with lysine-containing peptides and proteins
Ivancová, Ivana ; Hocek, Michal (advisor) ; Míšek, Jiří (referee) ; Urban, Milan (referee)
In the first part of this thesis, I developed reactive DNA probe for selective cross-linking with lysine residues of DNA-binding proteins. I synthesized 2'-deoxycytidine 5'-O-mono- and triphosphate bearing squaramate moiety tethered to the position 5 via propargylamine linker. The monophosphate was used as a model compound to test the reactivity of this mixed squaramate in cross-linking reactions with lysine and short lysine containing peptides. Squaramate modified 2'-deoxycytidine 5'-O-triphosphate was found to be suitable substrate for KOD XL polymerase in both PEX and PCR synthesis of modified DNA. Squaramate modified DNA forms stable diamide linkage with primary amines. I tested the reactivity of this DNA probe in bioconjugation reactions with sulfo-Cy5-amine and lysine containing peptides. Afterwards, squaramate-linked DNA was successfully cross-linked with lysine rich histone proteins. This reactive squaramate modified nucleotide showed potential for following bioconjugation reactions of nucleic acids with amines or lysine containing peptides and proteins without the need of external reagent. Based on positive results of experiments with squaramate modified DNA, in the second part of the thesis I developed and synthesized squaramate modified ribonucleotide to study cross- linking with RNA...
Novel fluorescent nucleotides for metabolic labelling and for the construction of DNA probes
Kuba, Miroslav ; Hocek, Michal (advisor) ; Slanina, Tomáš (referee) ; Míšek, Jiří (referee)
The aim of the thesis was to synthesize new nucleosides, nucleotides and the corresponding DNA probes bearing various fluorescent labels, which can be used for bioanalytical applications. In the first part of the thesis, 2'-deoxycytidine and the corresponding nucleoside triphosphate bearing tryptophan-based imidazolinone fluorophore were synthesized by Sonogashira cross-coupling reaction. The fluorophore showed sensitivity to pH and viscosity. Nucleotide was used for the construction of modified oligonucleotides (ON) and DNA by primer extension (PEX) or polymerase chain reaction (PCR). Labelled ON probe was used for sensing interaction with single-strand binding protein, which resulted in increased fluorescence intensity of modified ON. Next, thymidine and thymidine triphosphate labelled by bezylidene- tetrahydroxanthylium fluorophore were synthesized by copper-catalyzed azide-alkyne cycloaddition (CuAAC). Fluorescence of the fluorophore is dependent on the polarity and viscosity of the environment. Incorporation of the modified nucleotide into DNA, by PEX or PCR, led to dramatic increase of the fluorescence presumably due to the interactions of the fluorophore in the major groove. Unfortunately, the modified nucleotide was not suitable for in cellulo imaging due to its cytotoxicity. The modified...
Oxidative Post-translational Modifications and Their Importance
Šimková, Anna ; Míšek, Jiří (advisor) ; Petrák, Jiří (referee)
Aerobic life brings the inevitable exposure of living systems to reactive oxygen, nitrogen and chlorine species. A wide variety of oxidants can alter the structure of biomolecules such as proteins, lipids and DNA. Oxidative post-translational midifications play an important role in a number of cellular processes, for example, they are involved in redox signaling, gene transcription and metabolism. The increase of oxidants in cells leads to oxidative stress, which is associated with the development of neurodegenerative, cardiovascular and autoimmune diseases in humans. Considering reactive species as specific molecular agents can shed light on the complexity of the connection between redox processes and develop the emerging field of redox medicine.
Development of a synthetic methodology for the preparation of advanced cycloarenes and their analogues
Bambas, Daniel ; Stará, Irena (advisor) ; Míšek, Jiří (referee)
This Bachelor's Thesis deals with a design and preparation attempts leading to building blocks suitable for macrocycle construction with further utilization in cycloarene synthesis. In Theoretical Background methods for preparation of [n]circulenes and kekulene-like structures are summarized with focus on the final ring-closing steps. In Results and Discussion chapter efforts to prepare the selected advanced building block as a starting compound for macrocyle construction whose transformation using [2+2+2] cyclotrimerization as a ring-forming reaction might provide the selected cycloarene are described. Part Proposed alternatives of synthesis and discussion of further approach is about future possible development of this study. Experimental Part provides practical information about undertaken experiments and characterizations of the prepared compounds.
Using tandem cyclisation/Sonogashira cross-coupling in the synthesis of natural products and their derivatives
Liška, Benno ; Matoušová, Eliška (advisor) ; Míšek, Jiří (referee)
The subject of this bachelor's thesis is the preparation of polycyclic compounds using the tandem cyclisation/Sonogashira cross-coupling and a potential application of this reaction to the synthesis of natural products and their derivatives. The aim was to study this method using nonaromatic starting materials with a six-membered ring and to explore possibilities for functionalisation of the triple bond of the newly prepared compounds. The first part of this thesis deals with the synthesis of starting materials containing either an ether group or a malonate residue. The second part deals with the optimisation of conditions and the investigation of the scope of Heck reaction and Sonogashira cross-coupling. The third part describes the attempts to hydrate the triple bond and the last part contains reactions with allylic alcohols. Keywords: synthesis, tandem reaction, natural products, Sonogashira cross-coupling, Heck reaction
Design and Synthesis of cell nucleus-targeted compounds for use in bioorthogonal reactions
Hrušák, Jáchym ; Vrábel, Milan (advisor) ; Míšek, Jiří (referee)
This bachelor thesis focuses on the design and synthesis of 1,2,4,5-tetrazine and trans- cyclooctene derivatives containing functional moieties which are able to target cellular nucleus and participate in bioorthogonal reactions. Based on literature research, the targeting moieties and the structure of the tetrazine and trans-cyclooctene derivatives were designed with the aim to achieve selective nuclear targeting and to ensure sufficient reactivity of the resulting conjugates under biological conditions. Selected candidates were then synthesized and their properties together with cellular reactivity were investigated in model experiments.

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