Interakcije bis-benzotiazola supstituiranih amidinom s dvolančanim, trolančanim i hibridnim DNA:RNA polinukleotidima

master's thesis

• Title (english): Interactions of amidino-substituted bis-benzothiazoles with double-stranded, triple-stranded and hybrid DNA:RNA polynucleotides
• Author: Kristina Gunčević
• Mentor: Lidija-Marija Tumir (mentor)
• Committee member: Morana Dulić (predsjednik povjerenstva)
• Committee member: Sanda Rončević (član povjerenstva)
• Committee member: Mirta Rubčić (član povjerenstva)
• Committee member: Marko Močibob (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2023-02-16, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Derivati benzotiazola s amidinskim funkcionalnim skupinama pokazuju značajnu biološku
aktivnost. Četiri novosintetizirana derivata bis-benzotiazola supstituirana amidinom
spektroskopski su okarakterizirana te im je određena temperaturna stabilnost. Ispitane su
interakcije derivata bis-benzotiazola supstituiranih amidinom s DNA, RNA i hibridne
DNA:RNA polinukleotide. Kompeticijskom dijalizom probrani su polinukleotidi prema kojima
spojevi pokazuju najveći afinitet i selektivnost, te su oni korišteni u daljnjem istraživanju.
Eksperimenti temperature mekšanja pokazali su da benzotiazoli stabiliziraju dvolančane,
odnosno trolančane uzvojnice polinukleotida. Dodatak polinukleotida ispitivanim spojevima
uzrokovao je gašenje fluorescencije te su, na temelju fluorescencijskih titracija, izračunate ili
procijenjene konstante asocijacije. Spektri titracija dobiveni metodom cirkularnog dikroizma
ukazuju na mješovite načine vezanja; interkalaciju te vezanje u mali utor i agregiranje spoja
duž fosfatne okosnice. Dobiveni rezultati ukazuju na selektivnost spojeva prema određenim
sekvencama i strukturama nukleinskih kiselina.

Abstract (english)

Amidino-substituted benzothiazole derivates showed significant biological activity. Four newly
synthesized derivates of amidino-substituted bis-benzothiazoles were spectroscopically
characterized and their temperature stability was determined. Interactions of amidinosubstituted bis-benzothiazoles with DNA, RNA and hybrid DNA:RNA polynucleotides were
examined. Interaction of an array of polynucleotides with four benzothiazole derivates was
screened by competition dialysis. According to the screening results (affinities and selectivity)
polynucleotides were selected for detailed characterization. The thermal melting experiment
indicated that benzothiazoles stabilised double-stranded and triple-stranded polynucleotide
helixes. The addition of polynucleotide to the compound solution caused fluorescence
quenching. Association constants were calculated or estimated based on fluorimetric titrations.
Circular dichroism spectroscopy indicated mixed binding modes: intercalation, minor groove
binding and aggregation along the phosphate backbone. The obtained results indicated
benzothiazoles selectivity for specific polynucleotide sequences and structures.

• Keywords: benzotiazol; cirkularni dikroizam; DNA; DNA:RNA hibridi; fluorescencijska titracija; RNA; temperatura mekšanja
• Keywords (english): benzothiazole; circular dichroism; DNA; DNA-RNA hybrids; fluorescence titration; RNA; thermal melting
• Language: croatian
• URN:NBN: urn:nbn:hr:217:824911
• 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: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-02-16
• Created on: 2023-03-29 11:25:09