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HPLC evaluation of tyrosine and its metabolites
Michailellis, Panagiotis ; Kastner, Petr (advisor) ; Kučera, Radim (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Panagiotis Michailellis Supervisor: PharmDr. Petr Kastner, PhD. Title of Diploma Thesis: HPLC evaluation of tyrosine and its metabolites Tyrosine is an important precursor of catecholamines, which are dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). These are neurotransmitters and hormones, crucial for every living organism. Therefore, their identification and evaluation in biological material would aim to understand their function and behavior more accurately. This Diploma Thesis is a review on how to evaluate catecholamines and their metabolites in biological matter with analytical methods used in Pharmaceutical Analysis, especially with HPLC. First chapters present theoretical knowledge about metabolism of tyrosine and its metabolites, how a sample from an organism should be treated in order to be examined, information about HPLC, CE, GC apparatuses and the main detectors used in analysis of these compounds. In literature review, tables are presented, concerning different sample preparation methods, HPLC details and characteristics, and finally a sum of all the analytical methods studied for this Diploma Thesis. All the articles and...
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Molecular mechanism of DNA regulatory segment recognition by MADS box family transcription factors
Profantová, Barbora ; Štěpánek, Josef (advisor) ; Jelínek, Otakar (referee) ; Manfait, Michel (referee)
The thesis deals with physico-chemical properties of the MADS box, binding domain of transcription factors, which are important for the formation of complexes with the DNA regulatory segment bearing the CArG box. The study was performed also on model oligopeptides, selected segments of the MADS box and their analogues with a point mutation. A wide range of spectroscopic techniques was employed, namely absorption, circular dichroism, fluorescence and Raman spectroscopies. Advanced approaches including multivariate methods were used for data processing. The three tyrosines of the MADS box located in amino-acid vicinities of different charge and hydrophobicity, were used as intrinsic spectroscopic probes. The obtained characteristics of the MADS box and its segments structural arrangement, flexibility and acid-base equilibria are the main results of the work.
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A comparison of SH3 domains' tyrosine phosporylation influence on their binding capacity
Tatárová, Zuzana ; Novotný, Marian (advisor) ; Kuthan, Martin (referee)
Understanding the impact of protein phosphorylation is very important for the formation of dynamic biological processes such as gene silencing, cell growth, differentiation or apoptosis. This work deals with the phosphorylation of a protein-interaction module known as SH3 domain and the influence of phosphorylation on its ligand-binding capacity. SH3 domain is a part of a large number of enzymes directly involved in signal transduction as well as adapter proteins without enzymatic activity. Many studies have shown the importance of tyrosine sites within SH3 domain in regulatory mechanisms of proteins by using either mutants that cannot be phosphorylated, mutants mimicking the negative charges created by phosphorylation or by evidence of in vivo phosphorylation. The work also includes bioinformatic analysis, which further expand our knowledge of SH3 phosphorylated proteins and confirms that phosphorylation of the tyrosine sites is conserved among proteins containing the SH3 domain.
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Tyrosine-based prodrugs of acyclic nucleoside phosphonates
Tichý, Tomáš ; Pomeisl, Karel ; Krečmerová, Marcela ; McKenna, Ch. E.
Prodrug approach based on masking of a phosphonate function by ester linkage to a tyrosine promoiety has been developed. Results demonstrate that tyrosine is a promoiety providing drug conjugates with good chemical stability, bioavailability and efficient activation to active drug species. Another properties like metabolic stability and antiviral activity can be tuned by modification of the carboxyl function of the promoiety. Phosphonate monoester prodrugs were prepared by PyBOP coupling of a protected tyrosine promoiety with suitably derivatized phosphonate function of the parent drug. Phosphonate diester prodrugs were prepared by "synthon" approach, emloying alkylation of purine nucleobase with pre-prepared PME synthons bearing two protected tyrosine promoieties.
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Cyclic and acyclic phosphonate tyrosine ester prodrugs of acyclic nucleoside phosphonates
Williams, M. ; Krylov, I. S. ; Zakharova, V. M. ; Serpi, M. ; Peterson, L. W. ; Krečmerová, Marcela ; Kashemirov, B. A. ; McKenna, Ch. E.
A series of P-O ester derivatives of HPMPA, HPMPC, PMEA a (R)-PMPDAP was synthesized as potential anti-malarial prodrugs.
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