engleski

Interactions of novel amidino-substituted aryl- bis(benzazoles) with DNA/RNA

Series of eleven novel amidino-substituted bis(benzazoles), differing in heteroaromatic scaffolds as well as in type and position of amidine moiety, were studied for their binding abilities for DNA and RNA. By introducing different types of amidinic substituents and heteroaromatic substructure, namely benzothiazole, benzimidazole and benzoxazole, presented compounds were synthesized by condensation reaction of amidino-substituted 2- aminothiophenols, 2-aminophenols or o- phenylenediamines with isomeric aromatic dialdehydes or dicarboxylic acids by our previously developed method [1, 2]. Noncovalent binding interactions with DNA and RNA like intercalation, groove and electrostatic binding can be investigated by variety of methods. In order to detect possible presence of DNA/RNA active compounds in extracts, we utilized the most common methods in DNA binding studies: CD spectroscopy and the thermal denaturation of polynucleotides. While the former method monitors the impact of studied compounds on CD spectra of polynucleotides, the latter provides the information about the polynucleotide stabilization driven by compounds (ΔTm value). We used fluorimetry for the evaluation of the binding affinities. Competition dialysis experiment was used to probe the multitude of ligand-polynucleotide interactions. An array of different nucleic acid structures (single- stranded, double-stranded, DNA-RNA hybrid and triple helixes) were dialyzed against the compound solution for the assay. Dicationic compound 2-(2-(3-(6- carboximidamidiumbenzothiazole-2-yl)phenyl)- (benzothiazole-6-yl))-4, 5-dihydro-1H- imidazolium was identified as the most interesting one, as it showed high selectivity combined with high affinity over a particular polynucleotide structure. This compound was selected for detailed analysis with hybrid structure poly dA – poly rU by aforementioned methods.

amidines ; benzazoles ; interactions ; DNA/RNA

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