Karakterizacija vpliva aminokislinskih derivatov sukcinimida na aktivnost katepsina B

Turel, Tina (author), Novinec, Marko (mentor)

Katepsin B je predstavnik družine papainu podobnih cisteinskih peptidaz. Po svoji zgradbi se precej razlikuje od ostalih predstavnikov te družine, saj ima dodaten strukturni element, imenovan zaporna zanka. Zaporna zanka mu omogoča, da lahko deluje kot endo- ali eksopeptidaza. Endopeptidazna aktivnost katepsina B je povezana z različnimi patološkimi stanji, kot so revmatične bolezni. V okviru diplomskega dela smo preverjali vpliv nekaterih aminokislinskih derivatov sukcinimida na aktivnost človeškega katepsina B. Določili smo delež preostale encimske aktivnosti pri nasičenju z inhibitorjem ter potentnost inhibitorja v obliki vrednosti EC50. Iz nabora spojin smo identificirali spojine 6, 8 in 15, ki so delovale kot hiperbolični inhibitorji katepsina B ter 4, 5, 11 in 12, ki so delovale kot popolni inhibitorji. Izbranim inhibitorjem smo preverili tudi inhibitorni vpliv hidrolize makromolekulskega substrata azokazeina. Rezultati so pokazali, da so hiperbolični inhibitorji v večini obdržali svoje inhibitorne sposobnosti, linearni pa niso bistveno vplivali na razgradnjo azokazeina s katepsinom B.

• Language: Slovenian
• Keywords: katepsin B, alosterija, inhibitor, makromolekulski substrat
• Work type: Bachelor thesis/paper
• Typology: 2.11 - Undergraduate Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2019
• PID: 20.500.12556/RUL-109858
• COBISS.SI-ID: 1538391491
• Publication date in RUL: 09.09.2019

TUREL, Tina, 2019, Karakterizacija vpliva aminokislinskih derivatov sukcinimida na aktivnost katepsina B [online]. Bachelor’s thesis. [Accessed 29 June 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=109858

Secondary language

• Language: English

Abstract

Cathepsin B is a representative of the papain-like cysteine peptidase family. Its structure is different from the other representatives of this family, in that it has an additional structural element called the occluding loop. This element allows it to act as an endo- or exopeptidase. Endopeptidase activity of cathepsin B is involved in various pathological conditions, such as rheumatic diseases. In thesis, we tested the effects of selected amino acid derivatives of succinimide on the activity of human cathepsin B. We determined residual enzyme activity at saturation with inhibitors and the potency of the inhibitors expressed as EC50 were determined. From our in-house compound library, we identified compounds 6, 8 and 15, as partial inhibitors of cathepsin B and compounds 4, 5, 11 and 12 as linear inhibitors, respectively. Selected inhibitors were also assayed for their inhibitory effect on the hydrolysis of the macromolecular substrate azocaseins. Partial inhibitors, for the most part, retained their inhibitory activity, whereas linear inhibitors did not significantly affect the caseinolytic activity of cathepsin B.

• Keywords: cathepsin B, allostery, inhibitor, macromolecular substrate