engleski

Interactions of benzothiazole ligands with DNA:RNA hybrids and triplex structures

Nucleic acids are molecular targets for many drugs that are used in cancer therapy due to their essential functions in cells (replication, transcriptional and translational regulation, enzymatic reactions).1 Nucleic acid structures present a wide variety of shapes with varying major and minor groove widths that can be recognized by small molecules using a non-specific (mainly electrostatic) binding along the nucleic acid exterior, a specific groove binding and intercalation (insertion of planar aromatic molecules between base pairs).2 Interactions of an array of nucleic acid structures with a small series of benzothiazole ligands were screened by competition dialysis. The main aim of this study was the detection of benzothiazole-based moieties with selective binding or spectroscopic response to DNA:RNA hybrids and ATT triplex in regard to regular (non- hybrid) DNA and RNA duplexes and single-stranded forms. Complexes of nucleic acids and benzothiazoles, screened by this method, were then characterised by UV/Vis, fluorescence, circular dichroism (CD) spectroscopy and isothermal titration calorimetry. Compound 6 could differentiate between B- (binding of 6 dimers inside minor groove) and A-type (intercalation) helices by mode of binding while both 5 and 6 selectively stabilized ATT triplex regarding AT duplex. Compound 3 induced strong condensation- like changes in CD spectra of AT-rich DNA sequences.

DNA:RNA hybrids ; benzothiazole ligands ; ATT triplex ; interactions ; spectroscopy ; isothermal titration calorimetry

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