Paper in ChemBioChem

Dynamic chemistry of disulfide terminated oligonucleotides in duplexes and double-crossover tileschembiochem

De Stefano M, Gothelf K V

ChemBioChem, 2016, Marts 20

  • Department of Chemistry and iNANO, Center for DNA Nanotechnology, Aarhus University, Aarhus 8000, Denmark

Designed nanostructures formed by self-assembly of multiple DNA strands suffer from low stability at elevated temperature and under other denaturing conditions. Here, we propose a method to covalent coupling of all DNA strands in such structures by formation of disulfides, which also allows disassembly of the structure under reductive conditions. The dynamic chemistry of disulfides and thiols was applied to cross-link DNA strands with terminal disulfide modifications. The formation of disulfide linked DNA-duplexes consisting of three strands and a more complex DNA double-crossover tile is demonstrated. All the strands in the fully disulfide-linked structures are covalently and geometrically interlocked and it is demonstrated that the structures are stable towards heating and denaturants. Such a reversible system cab be exploited in applications where higher stability of DNA assemblies is needed only temporarily such as, for example, delivery of cargoes to cells by DNA nanostructures.