Razvoj metode na osnovi tekočinske kromatografije ultra visoke ločljivosti za ugotavljanje znotrajcelične koncentracije izbranih zaviralcev imunoproteasoma peptidnega tipa

Legan, Katja (author), Pajk, Stane (mentor), Gobec, Martina (comentor)

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.

• Language: Slovenian
• Keywords: UHPLC, imunoproteasom, peptidni zaviralci, PR957, DPLG3
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2020
• PID: 20.500.12556/RUL-113439
• Publication date in RUL: 07.01.2020

LEGAN, Katja, 2020, Razvoj metode na osnovi tekočinske kromatografije ultra visoke ločljivosti za ugotavljanje znotrajcelične koncentracije izbranih zaviralcev imunoproteasoma peptidnega tipa [online]. Master’s thesis. [Accessed 26 March 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=113439

Secondary language

• Language: English
• Title: Development of an ultra-high-performance liquid chromatography method for determination of intracellular concentrations of selected peptide type immunoproteasome inhibitors

Abstract

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.

• Keywords: UHPLC, immunoproteasome, peptide inhibitors, PR957, DPLG3