Reprogramming the assembly of unmodified DNA with a small molecule

The ability of DNA to store and encode information arises from base pairing of the four-letter nucleobase code to form a double helix. Expanding this DNA ‘alphabet’ by synthetic incorporation of new bases can introduce new functionalities and enable the formation of novel nucleic acid structures. However, reprogramming the self-assembly of existing nucleobases presents an alternative route to expand the structural space and functionality of nucleic acids. Here we report the discovery that a small molecule, cyanuric acid, with three thymine-like faces reprogrammes the assembly of unmodified poly(adenine) (poly(A)) into stable, long and abundant fibres with a unique internal structure. Poly(A) DNA, RNA and peptide nucleic acid all form these assemblies. Our studies are consistent with the association of adenine and cyanuric acid units into a hexameric rosette, which brings together poly(A) triplexes with a subsequent cooperative polymerization. Fundamentally, this study shows that small hydrogen-bonding molecules can be used to induce the assembly of nucleic acids in water, which leads to new structures from inexpensive and readily available materials

Supramolecular DNA nanotechnology : discrete nanoparticle organization, three-dimensional DNA construction, and molecule templated DNA assembly

The field of structural DNA nanotechnology utilizes DNA's powerful base-pairing molecular recognition criteria to help solve real challenges facing researchers in material science and nanotechnology, some of which include synthesis, sensing, catalysis, delivery, storage, optics, electronics, and scaffolding. In it, DNA is stripped away from any of its preconceived biological roles, and is treated as a powerful synthetic polymer. A subarea of research that our group has recently termed supramolecular DNA nanotechnology is emerging, and is proving to be a powerful complement to some of the already established rules of structural DNA nanotechnology. The work within this thesis falls under the umbrella of supramolecular DNA nanotechnology, and can conceptually be divided into three parts. (1) The first deals with the problem of discrete nanopartic1e organization. In it we present an approach for the facile and economical access to libraries of discrete nanoparticle assemblies that are addressable and switchable post-assembly. (2) The second deals with the synthesis of three-dimensional DNA assemblies. In it we present an approach for the facile construction of discrete three-dimensional DNA cages that can be structurally oscillated between pre-defined lengths, and adapt this approach to generate geometrically well-defined DNA columns of modular stiffness. (3) The last part deals with the use of small molecules to reprogram the assembly behavior of DNA. In it we use molecules to address the issue of error-correction, during and after the assembly process, and to facilitate the synthesis of "higher-order" DNA helices composed of more than two DNA strands. This work collectively offers a set of simple solutions to some of the bigger challenges currently facing researchers in DNA nanotechnology, and provides a snapshot of what is to be expected from tehe emerging discipline that is supramolecular DNA nanotechnology