Interactions of amidino-substituted bis-benzothiazoles with double-stranded, triple-stranded and hybrid DNA:RNA polynucleotides

Autor: Gunčević, Kristina
Přispěvatelé: Tumir, Lidija-Marija
Jazyk: chorvatština
Rok vydání: 2023
Předmět:
Popis: 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. 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.
Databáze: OpenAIRE