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Characterization of recombinant human serine racemase
Hoffman, Hillary Elizabeth ; Konvalinka, Jan (advisor) ; Křen, Vladimír (referee) ; Čeřovská, Noemi (referee)
6 Brief Abstract The pyridoxal-5'-phosphate-dependent enzyme serine racemase (SR) is responsible for the biosynthesis of D-serine in the mammalian central nervous system. D-serine acts as a neurotransmitter and coagonist, together with L-glutamate, of ionotropic N-methyl-D-aspartate receptors (NMDARs). Excitotoxic D-serine levels have been implicated in neuropathologies including Alzheimer's disease and amyotrophic lateral sclerosis. SR inhibitors offer a novel and potentially highly specific approach for attenuation of NMDAR-mediated glutamate excitotoxicity and for further study of the pathway. Many of the SR inhibitors described to date are small, naturally occurring compounds, and novel structures capable of influencing SR's activity are highly sought after. Moreover, structural information about this enigmatic enzyme is lacking, and suitable animal models need to be identified for inhibitor studies. This thesis presents the first published biochemical comparison of mouse and human SR orthologs, validating, at least in part, the use of mouse models in SR research. Additionally, hydroxamic acids are introduced as a novel class of SR inhibitors. While the experimentally determined structure of a mammalian SR remains elusive, random and site-directed mutagenesis experiments in combination with multiple...
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Electrochemistry of Flavonolignans and their Interactions with DNA and Proteins
Pyszková, M. ; Zatloukalová, M. ; Biedermann, David ; Křen, Vladimír ; Ulrichová, J. ; Ramešová, Šárka ; Sokolová, Romana ; Vacek, J.
Electrochemical oxidation of flavonolignans silybin, silydianin, silychristin and their 2,3-dehydroderivatives, was studied using ex situ and in situ cyclic and square wave voltammetry at pyrolytic graphite electrode. The pilot results presented here could be used for further investigation of mechanism of oxidation and reactivity of flavonolignans to DNA and proteins.
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Multivalentní glykokonjugáty ve studiu interakce lektinových receptorů NK/NKT buněk
Vannucci, Luca ; Pospíšil, Miloslav ; Rossmann, Pavel ; Chernyavskiy, Oleksandr ; Kubínová, Lucie ; Křen, Vladimír ; Luptovcová, Martina ; Svoboda, Jan ; Kuldová, Markéta ; Bezouška, Karel ; Fišerová, Anna
The events following the administration of GN8 in vitro, in vivo and ex vivo, lead to increased expression of CD69. The CD69-dependent IFNg production is modulated by co-activation of NKG2D and Ly49 receptors. Glycodendrimers can assist the dissection of activation network of NK/NKT cell lectin-like receptors in rat and murine models
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Multivalentní glykomika v imunoterapii experimentálních nádorů
Vannucci, Luca ; Pospíšil, Miloslav ; Krist, Pavel ; Křen, Vladimír ; Huliková, Katarína ; Luptovcová, Martina ; Svoboda, Jan ; Kuldová, Markéta ; Bezouška, Karel ; Rossmann, Pavel ; Difato, Francesco ; Mosca, F. ; Fišerová, Anna
Lectin-like receptors can modulate the cytotoxic, regulatory and dendritic cell responses by their interactions. GN8 multivalent glycoconjugates are able to internalize inside and activate NKR-P1 positive cells inducing production of IFN-gamma and expression of CD69. The final effect is a modulation of anticancer immunity with reduction of cancer growth
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