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Razvoj metode za ugotavljanje znotrajceličnih koncentracij izbranih zaviralcev imunoproteasoma psolarenskega tipa na osnovi tekočinske kromatografije ultra visoke ločljivosti
ID Debevc, Špela (Author), ID Pajk, Stane (Mentor) More about this mentor... This link opens in a new window, ID Gobec, Martina (Co-mentor)

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Abstract
Immunoproteasom je znotrajcelična proteaza, katere glavna fiziološka funkcija je, da razgrajuje nepravilno zvite in poškodovane proteine. Zaviranje proteolitične aktivnosti imunoproteasoma bi lahko bilo ugodno pri zdravljenju nekaterih rakavih obolenj oz. avtoimunih bolezni. Izbrani zaviralci imunoproteasoma niso izkazovali predvidenega učinka na celični liniji, za kar je lahko kriva premajhna znotrajcelična koncentracija zaviralca. Izbrani zaviralci so namreč zelo lipofilni in ker gre za kovalentne zaviralce, lahko tudi reagirajo s proteini v celičnem mediju. V magistrski nalogi bomo poizkusili razviti metodo na osnovi UHPLC za ugotavljanje intracelularne koncentracije izbranih zaviralcev.

Language:Slovenian
Keywords:Imunoproteasom, kovalentni zaviralci, tekočinska kromatografija ultra visoke ločljivosti, LR057, GBB102
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2019
PID:20.500.12556/RUL-113295 This link opens in a new window
Publication date in RUL:19.12.2019
Views:910
Downloads:229
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Secondary language

Language:English
Title:Development of an ultra-high-performance liquid chromatography method for determination of intracellular concentrations of selected psolaren-based immunoproteasome inhibitors
Abstract:
Immunoproteasome is an intracellular protease, whose pivotal role is degradation of abnormally folded and damaged proteins. Inhibition of the proteolytic activity of the immunoproteasome could be advantageous in the treatment of certain cancers and autoimmune diseases. The selected immunoproteasome inhibitors did not show the intended effect on the cell line, which may be due to the insufficient intracellular inhibitor concentration. The selected inhibitors are very lipophilic and because they are covalent inhibitors, they can also react with proteins in the cell medium. In the master's thesis we will try to develop a method based on UHPLC to determine the intracellular concentration of selected inhibitors.

Keywords:Immunoproteasome, covalent inhibitors, ultra-high-performance liquid chromatography, LR057, GBB102.

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