20.500.12556/RUL-113439 Razvoj metode na osnovi tekočinske kromatografije ultra visoke ločljivosti za ugotavljanje znotrajcelične koncentracije izbranih zaviralcev imunoproteasoma peptidnega tipa Development of an ultra-high-performance liquid chromatography method for determination of intracellular concentrations of selected peptide type immunoproteasome inhibitors Imunoproteasom je del natančno nadzorovanega ubikvintin–proteasomskega sistema, ki se izraža predvsem v imunskih celicah, kjer sodeluje pri vzdrževanju celičnega homeostaznega ravnovesja. Njegovo zaviranje velja za že dobro uveljavljeno terapijo številnih avtoimunskih, rakavih in nevrodegenerativnih obolenj. Namen te magistrske naloge je bil razvoj UHPLC analitske metode za ugotavljanje znotrajcelične koncentracije PR957 in DPLG3, peptidna zaviralca imunoproteasoma. Z merjenjem meje detekcije in kvantifikacije, topnosti, stabilnosti in koncentracije v celičnem gojišču, smo poskušali poiskati vzrok njune neaktivnosti na celični liniji. Immunoproteasome is a part of well-controled ubiquintin-proteasome system, that is expressed mainly in immune cells and collaborates in degredation of damaged proteins. In this way it significantly contributes to the maintenance of normal cell homeostasis balance. Its inhibition is considered to be a well-established therapy for many avtoimmune, cancer and neurodegenerative diseases. The purpose of this master thesis was to develop an UHPLC analytical method to determine the intracelullar concentration of PR957 and DPLG3, peptide type imunoproteasome inhibitors. There was a lack of effect on cells and the reason for this may be too small intracellular concentration of both, because of e.g. degradation or difficulty in crossing plasma membrane. The determination of intracellular concentrations may help determine the reason for the lack of effect. UHPLC imunoproteasom peptidni zaviralci PR957 DPLG3 UHPLC immunoproteasome peptide inhibitors PR957 DPLG3 true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2020-01-07 08:35:09 2020-01-07 08:35:13 2022-08-25 03:56:22 0000-00-00 00:00:00 2020 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 72691 863.pdf 863.pdf 1 0447006B3982D9845872A200D74DAD1E 785c8dc346cbf477cc43ff498b11b6f8d65a9ad32b67f40195793bfe10f7e626 1b2fc4b3-a1b8-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=125527 Fakulteta za farmacijo 0 0 0