Termodinamika konformacijskih sprememb G-kvadrupleksov z zaporedjem d(G4T4G4)

Žigante, Nataša (author), Prislan, Iztok (mentor)

G-kvadrupleksne strukture, ki se tvorijo v telomernih regijah, predstavljajo obetavno tarčo za razvoj potencialnih novih učinkovin za zdravljenje različnih tipov bolezni. Za razvoj le-teh je ključno poznavanje strukture G-kvadrupleksov in njihove stabilnosti. V magistrskem delu smo preučili strukturo modelnih G-kvadrupleksov z zaporedjem d(G4T4G4) in njihove stabilnosti ob prisotnosti kalijevih, natrijevih in kalcijevih ionov. V ta namen smo uporabili CD-spektropolarimertrijo, DSC in gelsko elektroforezo. Potrdili smo, da zaporedje d(G4T4G4) lahko tvori paralelno, antiparalelno ali hibridno konformacijo v odvisnosti od vrste in koncentracije ionov oz. lastnosti prisotnega topila. Ob prisotnosti različnih ionov lahko pride do prehajanja iz ene strukture v drugo. Za opis eksperimentalnih podatkov DSC termograma razvitja G-kvadrupleksne strukture ob prisotnosti kalijevih ionov v vodi smo postavili enostaven model, s katerim zadovoljivo popišemo razvitje strukture pri različnih hitrostih gretja.

• Language: Slovenian
• Keywords: G-kvadrupleks, termodinamika, modelna funkcija
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2019
• PID: 20.500.12556/RUL-109651
• COBISS.SI-ID: 1538399683
• Publication date in RUL: 06.09.2019

Secondary language

• Language: English
• Title: Thermodynamics of conformational changes of d(G4T4G4) G-quadruplex structures

Abstract

G-qudruplex structures, which are formed in telomere regions, represent a promising target for potential development of new active substances for curing different types of diseases. Understanding the G-quadruplex structures and their stability is crucial for their development. In my master’s thesis I have studied these G-quadruplex d(G4T4G4) structures and their stability in the presence of potassium, sodium and calcium ions. Four our study of d(G4T4G4) we used CD-spectropolarimetry, DSC and gel electrophoresis. We confirmed that d(G4T4G4) sequences can form a parallel, antiparallel or hybrid conformation depending on the type and concentration of ions and solvent properties. The presence of these different ions can lead to transformation from one structure to another. To describe the experimental data of the DSC thermogram, we proposed a kinematic model, that describes thermally induced conformational transition of water diluted d(G4T4G4) in the presence of potassium ions at different heating rates.

• Keywords: G-quadruplex, thermodynamics, model function