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master's thesis
Stvaranje kristalne strukture kimernih molekula faktora rasta EGF receptora
2022. urn:nbn:hr:171:990899
Žuljević Escobar, Sara
University of Split
School of Medicine

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Žuljević Escobar, S. (2022). Stvaranje kristalne strukture kimernih molekula faktora rasta EGF receptora (Master's thesis). Split: University of Split, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:171:990899

Žuljević Escobar, Sara. "Stvaranje kristalne strukture kimernih molekula faktora rasta EGF receptora." Master's thesis, University of Split, School of Medicine, 2022. https://urn.nsk.hr/urn:nbn:hr:171:990899

Žuljević Escobar, Sara. "Stvaranje kristalne strukture kimernih molekula faktora rasta EGF receptora." Master's thesis, University of Split, School of Medicine, 2022. https://urn.nsk.hr/urn:nbn:hr:171:990899

Žuljević Escobar, S. (2022). 'Stvaranje kristalne strukture kimernih molekula faktora rasta EGF receptora', Master's thesis, University of Split, School of Medicine, accessed 06 April 2025, https://urn.nsk.hr/urn:nbn:hr:171:990899

Žuljević Escobar S. Stvaranje kristalne strukture kimernih molekula faktora rasta EGF receptora [Master's thesis]. Split: University of Split, School of Medicine; 2022 [cited 2025 April 06] Available at: https://urn.nsk.hr/urn:nbn:hr:171:990899

S. Žuljević Escobar, "Stvaranje kristalne strukture kimernih molekula faktora rasta EGF receptora", Master's thesis, University of Split, School of Medicine, Split, 2022. Available at: https://urn.nsk.hr/urn:nbn:hr:171:990899

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Metadata
TitleStvaranje kristalne strukture kimernih molekula faktora rasta EGF receptora
Title (english)Crystal structure modelling of the chimeric growth factor molecules of the EGF receptor
AuthorSara Žuljević Escobar
MentorJasminka Omerović (mentor)
Committee memberAnita Markotić (predsjednik povjerenstva)
Committee memberVedrana Čikeš Čulić (član povjerenstva)
Committee memberJasminka Omerović (član povjerenstva)
GranterUniversity of Split
School of Medicine
Split
Defense date and country2022-10-27, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Immunology
Abstract
Heterogeni izražaj molekula faktora rasta u tumorskim tkivima jedan je od čestih uzroka de novo rezistencije. Liječenje tumora ovisnih o signalima EGF receptora primarno je usmjereno na inhibiciju aktivacije receptora vezanih za istovrsne molekule faktora rasta. Shodno tome, izostavljeno je u cijelosti djelovanje heterogenog izražaja molekula faktora rasta u tumorskom tkivu. U cilju istraživanja djelovanja izražaja različitih faktora rasta na razvoj i rezistenciju tumora, izrađene su uz pomoć... More računalnih programa i alata, PyMOL i PyMod 3, strukture proteinskih kimernih molekula građene od dvije molekule faktora rasta EGF receptora, međusobno povezane fleksibilnim ili krutim povezivačem. Aminokiselinski slijed oba povezivača (fleksibilni ili GG-GSAT*-GG i kruti ili GGG-MYO6*-GGG) modificiran je kako bi se omogućila bolja fleksibilnost kimerne molekule te je dodatno slijed aminokiselina krutog povezivača skraćen kako bi se optimizirala udaljenost između dvije molekule faktora rasta. Sekvence kimernih molekula analizirane su koristeći PyMOL i ProtParam; analizirana je molekularna masa, teorijski pI, hidrofobnost, indeks nestabilnosti i alifatski indeks kimernih molekula. Prema dobivenim podacima može se zaključiti da model Kimera 1 ima najbolju termostabilnost, Kimera 3 ima najviši pI, a Kimera 2 se pokazao kao najhidrofilniji od svih modela. Predviđena stabilnost kimernih modela koji sadrže fleksibilni povezivač bila je veća u odnosu na modele s krutim povezivačem. Modeliranje struktura kimernih molekula s fleksibilnim povezivačem moglo bi rezultirati boljim razumijevanjem utjecaja heterogenog izražaja molekula faktora rasta, dok bi kimerne molekule s krutim povezivačem mogle spriječiti aktivaciju receptora. U konačnici, ovo bi bili ključni alati za istraživanja rasta, razvoja i rezistencije samoga tumora, te inhibicije tumorigeneze. Less
Abstract (english)
Heterogeneous expression of growth factor molecules in tumor tissues is one of the most frequent causes of de novo resistance. Treatment of EGFR signal-dependent tumors primarily targets the inhibition of receptor activation induced by two growth factor molecules. Thus, the heterogeneous expression of growth factor molecules in tumor tissue was ignored. In order to investigate the effect of the expression of different growth factors on tumor growth and resistance, with the help of computer... More programs and tools, PyMOL and PyMod 3, we modelled chimeric protein structures harbouring two molecules of growth factors of EGF receptor, interconnected with a flexible or rigid linker. The protein sequences of both linkers (flexible or GG-GSAT*-GG and rigid or GGG-MYO6*-GGG) were modified to improve the mobility of the chimeric molecule and the rigid linker was further shortened to optimize the distance between the two growth factor molecules. The protein sequences of chimeric molecules were analyzed using PyMOL and ProtParam, and the protein molecular mass, theoretical pI, hydrophobicity, instability index, and aliphatic index of chimeric molecules were determined. According to the obtained data, the model Chimera 1 has the best thermostability, Chimera 3 has the highest pI value, and Chimera 2 proved to be the most hydrophilic of all models. The predicted stability of the chimeric models containing a flexible linker was higher than that of models with a rigid linker. Modelling the structures of chimeric molecules with a flexible linker could result in a better understanding of the impact of heterogeneous expression of growth factor molecules, whereas chimeric molecules with a rigid linker could prevent receptor activation. In conclusion, these would be the key research tools by which we could define the mechanisms of microenvironment impact on tumor growth, progression, and resistance, as well as tumor inhibition. Less
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:171:990899
Study programmeTitle: Pharmacy
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2022-10-31 08:39:10
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