Molekulsko prepoznavanje hibridnih i višelančanih struktura DNA i RNA

doctoral thesis

• Title (english): Molecular recognition of hybrid and multistranded DNA and RNA structures
• Author: Iva Zonjić
• Mentor: Marijana Radić Stojković (mentor)
• Mentor: Lidija-Marija Tumir (mentor)
• Committee member: Snežana Miljanić (predsjednik povjerenstva)
• Committee member: Nikola Basarić (član povjerenstva)
• Committee member: Aleksandar Višnjevac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2023-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

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.

Abstract (english)

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.

• Keywords: DNA; benzotiazolni derivati; cijaninske boje; fenatridinski derivati; hibridne strukture nukleinskih kiselina; RNA; višelančane strukture nukleinskih kiselina
• Keywords (english): DNA; benzotiazole derivatives; cyanine dyes; hybrid nucleic acid structures; multistranded nucleic acid structures; phenanthridine derivatives; RNA
• Language: croatian
• URN:NBN: urn:nbn:hr:217:957466
• Promotion: 2023
• Project: Number: IP-2018-01-4694; Title: Molekularno prepoznavanje DNA:RNA hibridnih i višelančanih struktura u bioanalitičkim i in vitro sustavima; Acronym: DNARNAHyB-MolBio; Leader: Marijana Radić Stojković; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Doctoral study in chemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
• Type of resource: Text
• Extent: 122, XVIII str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-07-20 11:59:08