New photoswitches for the reversible modulation of DNA and RNA

• Applicant: Professor Dr. Andres Jäschke
• Subject Area: Biological and Biomimetic Chemistry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 529549043

The reversible modulation of DNA and RNA function by light holds great significance for the advancement of bionanotechnology, photopharmacology, super-resolution microscopy, and next-generation computing. Our group has introduced new classes of nucleoside-based diarylethenes (DAEs) and optimized them for high-performance photoswitching. Initial applications at the macromolecular level have been explored. Our long-term objective is to achieve control over the structure and the catalytic, substrate, or regulatory functions of DNA and RNA in a flexible and comprehensive manner. To accomplish this goal, we propose to: i. Generate improved photoswitchable fluorescence with nucleosidic DAEs. ii. Develop dA and dU DAE switches that can be switched with visible light. iii. Optimize dG and dC DAE switches. iv. Create combinatorial methods for determining the optimal positions for photomodulation of deoxyribozymes and DNA aptamers. v. Synthesize and characterize ribo versions of the optimized deoxyribo DAEs. vi. Conduct first proof-of-principle experiments to study DAE-functionalized RNA. vii. Devise combinatorial methods for identifying the optimal positions for photomodulation of ribozymes and RNA aptamers. This work will enable applications in the fields mentioned above.

• DFG Programme: Research Grants