The proposed project aims at the development of novel functional ligands whose association with ribonucleic acid (RNA) is reversibly activated by light. As several RNA forms are essential key elements in physiological processes, the control of their function or malfunction by the reversible binding of photoswitchable ligands possesses a great potential as a tool in anticancer, antiviral and antimicrobial therapy. Surprisingly, this innovative approach towards a controlled reversible generation of RNA binders was mainly neglected in this highly topical research field. Hence, in this project photochromic hemi-indigo and fulgide derivatives are chosen as a platform for the design of photo-responsive RNA ligands, because i) they exhibit general features of RNA binders; ii) their structure can be reversibly modified by light, iii) the core structures are readily synthesized, and iii) the substitution pattern can be easily varied to enable fine-tuning of binding selectivity based on structure-activity relationships. In addition, conjugates that comprise two photoactive RNA-binding units will be obtained and studied because such bifunctional binders are expected to have very high affinity and selectivity toward RNA. An extensive library of derivatives will be synthesized and tested for their photocontrollable association with RNA. As a special method, real-time NMR-spectroscopic studies with direct irradiation of the sample inside a specifically designed spectrometer will be used to assess in detail the dynamics in the course of the photoinduced ligand–RNA interactions. Overall, it is anticipated that this systematic approach will enable the identification and development of lead structures for controllable RNA-targeting drugs with a great pharmacological potential. Moreover, the high interdisciplinary, innovative character of this challenging project gives the researcher an excellent opportunity to achieve professional maturity and open up best career possibilities.
Fields of science
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural scienceschemical sciencesphysical chemistryphotochemistry
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesHIV
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesgeneticsRNA