Multifunctional molecular sensing of DNA/RNA secondary structure by chemical sensors
Molecular recognition of DNA/RNA 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 but also for potential medicinal applications, as sensors or probes for fluorescence based bioimaging as well as for analytical purposes in isolated biosamples. Proposal is based on the collaboration between I. Piantanida and Prof. Dr. C. Schmuck (Germany), joined results in leading chemistry journals (Chemistry, Eur. J; 2010 and 2012, J. Am. Chem. Soc. 2012; Org. Biomol. Chem. 2011, Bioorg. Med. Chem. Lett. 2008). We want to design, synthesize and study highly selective probes for the sensing of DNA/RNA with 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. For increased affinity and selectivity, we plan to test new, more efficient fluorophores (cyanine, phenanthridine, fluorescent nucleobases-Piantanida group) combined with pyrrole-guanidinium cations (Schmuck group) and explore structural diversity of the compounds, by combinatorial approach (solid phase synthesis) based on peptide backbone carrying recognition units/fluorophores. The interaction with DNA/RNA will be studied by Piantanida group (UV/Vis, fluorescence, CD/LD spectroscopy, DSC/ITC microcalorimetry), screening of oligopeptide libraries by IRORI method and atomic force microscopy by Schmuck group. Proposal addresses CSF goals: a) support the collaboration with well-established international leaders, b) foster training of young researchers by work on the INTERNATIONAL research; c) expected results with commercializing potential (novel biochemical probes and/or drugs). The latter feature (c) will be studied within FP7-REGPOT “Innomol” Project at Ruđer Bošković Institute.