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

Mattia De Stefano, Kurt Vesterager Gothelf

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Abstract

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 for covalent coupling of DNA strands in such structures by the formation of disulfide bonds; this allows disassembly of the structure under reducing conditions. The dynamic chemistry of disulfides and thiols was applied to crosslink DNA strands with terminal disulfide modifications. The formation of disulfide-linked DNA duplexes consisting of three strands is demonstrated, as well as a more-complex DNA double-crossover tile. All the strands in the fully disulfide-linked structures are covalently and geometrically interlocked, and it is demonstrated that the structures are stable under heating and in the presence of denaturants. Such a reversible system can be exploited in applications where higher DNA stability is needed only temporarily, such as delivery of cargoes to cells by DNA nanostructures.

Original languageEnglish
JournalChemBioChem
Volume17
Issue12
Pages (from-to)1122-1126
Number of pages5
ISSN1439-4227
DOIs
Publication statusPublished - 20 Mar 2016

Keywords

  • DNA structures
  • disulfides
  • dynamic combinatorial chemistry
  • nucleic acids
  • reduction

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