diplomsko delo
Urban Hribar (Author), Marko Novinec (Mentor)

Abstract

Katepsin V spada med katepsinu L podobne katepsine iz družine papainu podobnih peptidaz. Je cisteinska lizosomska endopeptidaza, ki jo najdemo le pri višjih primatih. Izraža se v specifičnih tkivih, predvsem v priželjcu, kjer ima pomembno vlogo pri predstavitvi antigenov. Pri diplomski nalogi smo pregledali knjižnico spojin, ki so bile sintetizirane kot potencialni alosterični inhibitorji katepsinov K in S, in med njimi želeli poiskati alosterične inhibitorje katepsina V. Inhibicijske lastnosti smo določili iz kinetičnih meritev, narejenih z uporabo fluorimetrije. Znotraj knjižnice spojin na žalost nismo uspeli najti nobenega dobrega alosteričnega inhibitorja. Tri najbolj obetavne spojine smo uporabili za titracijo katepsina V, pri čemer smo ugotovili, da ti najverjetneje ne kažejo hiperbolične inhibicije, ki je bila opažena pri alosteričnih inhibitorjih katepsina K, in najverjetneje nimajo alosteričnega mehanizma. Te tri spojine smo tudi računalniško umestili na alosterično in aktivno mesto katepsina V s pomočjo algoritma Autodock Vina 1.1.2. Prav tako smo izmerili inhibicijo encimske razgradnje elastina za eno izmed treh spojin.

Keywords

encimi;peptidaze;cisteinski katepsin;katepsin V;alosterična inhibicija;encimska kinetika;makromolekulski substrat;računalniško prileganje spojin;diplomska dela;

Data

Language: Slovenian
Year of publishing:
Typology: 2.11 - Undergraduate Thesis
Organization: UL FKKT - Faculty of Chemistry and Chemical Technology
Publisher: [U. Hribar]
UDC: 577.152.34(043.2)
COBISS: 1538391747 Link will open in a new window
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Downloads: 164
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Other data

Secondary language: English
Secondary abstract: Cathepsin V is a cathepsin L-like peptidase from the papain-like cysteine peptidase family. It is a lysosomal peptidase found only in higher primates. It is expressed only in specific tissues, primarily in the thymus where it plays a major role in antigen presentation. Our goal for this assignment was to identify allosteric inhibitors from a library of compounds designed as alosteric inhibitors of cathepsins K and S. The inhibitory properties of the compounds were inferred from the results of enzyme kinetic measurements taken using fluorometry. Unfortunately, we managed to find no good allosteric inhibitors from the library. We used the three most promising inhibitor compounds for titration of cathepsin V, which did not act as hyperbolic inhibitors as observed for allosteric inhibitors of cathepsin K, and are therefore likely not allosteric. Using the molecular docking algorithm Autodock Vina we docked all three compounds into the active site and allosteric site of cathepsin V. We also measured the inhibitory activity of one compound on the degradation of soluble elastin.
Secondary keywords: cathepsin V;alosteric inhibition;enzyme kinetics;macromolecular substrate;computer docking;
Type (COBISS): Bachelor thesis/paper
Study programme: 1000371
Embargo end date (OpenAIRE): 1970-01-01
Thesis comment: Univ. v Ljubljani, Fak. za kemijo in kemijsko tehnologijo, UNI Biokemija
Pages: III, 27 str.
ID: 11219427