Molekulsko prepoznavanje hibridnih i višelančanih struktura DNA i RNA
Autor: | Zonjić, Iva |
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Přispěvatelé: | Radić Stojković, Marijana, Tumir, Lidija-Marija |
Jazyk: | chorvatština |
Rok vydání: | 2023 |
Předmět: |
fenatridinski derivati
cyanine dyes cijaninske boje phenanthridine derivatives DNA hybrid nucleic acid structures PRIRODNE ZNANOSTI. Kemija NATURAL SCIENCES. Chemistry hibridne strukture nukleinskih kiselina benzotiazole derivatives RNA multistranded nucleic acid structures udc:54(043.3) Kemija. Kristalografija. Mineralogija benzotiazolni derivati višelančane strukture nukleinskih kiselina Chemistry. Crystallography. Mineralogy |
Popis: | Male molekule koje se preferencijalno vežu za hibridne i višelančane strukture DNA i RNA nekovalentnim interakcijama od velikog su znanstvenog interesa, te mogu naći primjenu kao novi i bolji dijagnostički i terapeutski alati. Iako te strukture imaju važnu biološku funkciju unutar stanice mali je broj liganada koji se na njih preferencijalno vežu. Cilj ovog rada je pronaći nove strukturne motive/spojeve koji se preferencijalno vežu na hibridne i višelančane u odnosu na regularne DNA i RNA strukture. Ispitano je nekoliko grupa spojeva: benzotiazolni derivati i cijaninske boje koje su dobivene u suradnji s drugim istraživačkim grupama. Također, istražene su interakcije novosintetiziranih fenantridinskih derivata s DNA. Spojevi s preferencijalnim vezanjem na hibridne i višelančane strukture DNA i RNA odabrani su pomoću brzih metoda probira-kompeticijske dijalize i temperaturnog mekšanja smjesa te RNaza H testa. Daljnjim bioanalitičkim metodama (spektroskopija UV/Vis, fluorescencijska spektroskopija i cirkularni dikroizam) detaljno su okarakterizirane interakcije vezanja malih molekula s odabranim metama. Pokazali smo da se benzotiazolski i cijaninski derivati preferencijalno vežu na hibridne i višelančane strukture DNA i RNA u odnosu na regularne što bi se moglo iskoristiti u antitumorskoj terapiji i za detekciju struktura nukleinskih kiselina. Small molecules able to preferentially bind to specific hybrid and multistranded structures of DNA and RNA by non-covalent interactions are of great scientific interest when it comes to obtaining new and better diagnostic and therapeutic tools. Although these structures have an important biological function inside the cell, there is only a few known ligands which preferentially bind to them. The goal of this thesis is to find new structural motifs/compounds that preferentially bind to hybrid and multistranded structures compared to regular DNA and RNA structures. A small library of several groups of compounds was formed: benzothiazole derivatives and cyanine dyes obtained in collaboration with other research groups. Also, interactions of newly synthesized phenanthridine derivatives with DNA were investigated. Compounds with preferential binding to hybrid and multistranded structures of DNA and RNA were selected using competitive dialysis as a rapid screening method, as well as with melting of mixtures and RNase H assay. Further bioanalytical methods (flourescence and UV/Vis spectroscopy and circular dichroism) were used to characterize their binding interactions with selected targets in detail. The obtained results indicate that certain derivatives from the mentioned classes of compounds preferentially bind to hybrid and multistranded structures of DNA and RNA compared to regular ones, which opens the possibility of their application in antitumor therapy and for the detection of nucleic acid structures. |
Databáze: | OpenAIRE |
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