Multifunctional molecular sensing of DNA/RNA secondary structure by chemical sensors - DNA/RNA-MolSense
Molecular recognition of nucleic acids is of fundamental importance e.g. for gene transcription and regulation, protein synthesis or cell-division. Small molecules selectively targeting specific DNAs or RNAs are therefore highly interesting not only to understand such processes in more detail on a molecular level but also for potential medicinal applications, as sensors or probes for fluorescence based bioimaging as well as for analytical purposes in isolated biosamples.
In this project we want to design, synthesize and study highly selective probes for the sensing of nucleic acid secondary structures with special emphasis on the multi-purpose probes: single molecules able to simultaneously differentiate by several highly sensitive spectrometric methods between the most common secondary structures of ds- DNA/RNA. To develop compounds with increased affinity and selectivity and more pronounced fluorimetric responses, we plan to test new, more efficient fluorophores (cyanine, phenanthridine, fluorescent nucleobase derivatives - Piantanida group) combined with pyrrole-guanidinium cations (partner from Duisburg-Essen University; Schmuck group) and explore structural diversity of the compounds, using a combinatorial approach based on peptide backbone carrying recognition units prepared by solid phase synthesis. The interaction with DNA/RNA will be studied by Piantanida group (UV/Vis, fluorescence, CD/LD spectroscopy, viscometry and DSC/ITC microcalorimetry, MS, NMR, X-ray, CLSM), while expertise not available in Croatia (pyrrole-guanidinium coupling, oligopeptide libraries screening) will be performed in collaboration with Schmuck group.