Ligand-templated assembly of aptamers and ribozymes from short borono-based nucleic acids sequences

• Applicant: Professorin Dr. Sabine Müller
• Subject Area: Biological and Biomimetic Chemistry ; Biochemistry ; Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 316800023

The predictable nature of nucleic acid hybridization offers a simple and cutting-edge platform to program assemblies with emerging function. While nucleic acids are known to be versatile biomolecules that play a crucial role in regulating gene expression in various organisms, the burgeoning use of nucleic acids as a material to organize the precise arrangements of specific molecules marked an important milestone in the relatively young history of smart bioarchitectures. While functional DNAs and RNAs hold great promise for future applications in nanotechnology and bioanalysis, in this project, we set out to design and study functional stimuli-responsive nucleic acids-based architectures, capable of self-assembling by formation of reversible linkages. Based on the complementary expertise of the two partners, the main goal of the present project is to induce the self-assembly of small aptamers, ribozymes and aptazymes from short DNA or RNA fragments modified with a 5'-boronic acid, and to demonstrate their functionality. With respect to possible application of our results, we see potential in the field of biosensing; a system composed of a collection of 5'-boronic acid modified oligonucleotides could be used for detection/sensing of a chosen analyte. We consider our work being relevant not only for the field of biosensing, but moreover for investigations into RNA world scenarios, where self-organization and self-assembly of smaller oligonucleotides to larger functional entities might have played an important role. As has been hypothesized, boronic acids forming reversible linkages with the cis-diol of ribose may have preceded RNA phosphate linkages, and the demonstration of boronic acid linkage based self-assembly would strongly support this idea.

• DFG Programme: Research Grants
• International Connection: France
• Partner Organisation: Agence Nationale de la Recherche / The French National Research Agency
• Cooperation Partner: Professor Dr. Michael Smietana