Molecular recognition of DNA:RNA hybrid and multistranded structures in bioanalytical and in vitro systems - DOK
Principal investigator
DNA:RNA hybrid and multistranded structures are formed as intermediate structures during many biologically important processes such as DNA replication, transcription, telomere replication and replication of HIV virus. Therefore, they represent attractive targets for small molecules, especially since the literature citations of the ligands with selective binding to these targets are scarce. To fulfill the main project goal, the search for new structural motives/compounds with preferential binding to DNA:RNA hybrid and multistranded structures vs. regular DNA and RNA duplexes and single-stranded structures, other aims have to be fulfilled first: forming a library of compounds, with structural motif necessary for interaction with these targets, introduction and implementation of new DNA and RNA targets (DNA:RNA hybrid and multistranded structures) and high-throughput methods (competition dialysis, thermal denaturation of mixtures, RNaseH assay) in the research study of our project team, which would enable fast screening of compounds for recognition of these targets. Another aim is to investigate in detail the mode of binding of selected ligand-DNA/RNA complexes in bioanalytical systems (aqueous buffered solutions) by spectroscopic, calorimetric and computational methods. Further, we will investigate the possible correlation between the strong binding potential of selected compounds and their antiproliferative activity in cell culture (MTT, flow cytometry, confocal microscopy).Expected results, fulfillment of the above-mentioned aims can be utilized for: broadening of the basic knowledge in the research area, optimisation of the ligands structure with the goal of improving the binding selectivity to desired DNA and RNA targets, possible medicinal use, strengthening of the inter-organizational collaboration in Croatia and development of novel research expertise that would enable publishing in quality scientific journals.