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Reprogramming the assembly of unmodified DNA with a small molecule

Nature Chemistry volume 8, pages 368–376 (2016)Cite this article

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Abstract

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 (PNA) 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.

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Figure 1: CA-mediated assembly of d(An).
Figure 2: Proposed hexameric rosette structure.
Figure 3: Fibre elongation mode.
Figure 4: Mechanism of supramolecular polymerization.
Figure 5: Thermal denaturation studies monitored by CD at 252 nm.
Figure 6: CA-mediated assembly of other oligonucleotides (RNA, PNA) and fibre functionalization.

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Acknowledgements

We acknowledge the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canada Research Chairs Program, the Canada Foundation for Innovation, the Centre for Self-Assembled Chemical Structures and the Canadian Institute for Advanced Research for financial support. N.A. and A.G. thank NSERC and Fonds Québécois de la Recherche sur la Nature et les Technologies for doctoral fellowships. C.J.S. thanks NSERC for a Banting Postdoctoral Fellowship. H.F.S. is a Cottrell Scholar of the Research Corporation.

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Authors and Affiliations

  1. Department of Chemistry and Centre for Self-assembled Chemical Structures, McGill University, 801 Sherbrooke Street West, Montreal, H3A 0B8, Quebec, Canada

    Nicole Avakyan, Andrea A. Greschner, Faisal Aldaye, Christopher J. Serpell, Violeta Toader & Hanadi F. Sleiman

  2. INRS: Centre Énergie Matériaux Télécommunications, 1650 Boul. Lionel-Boulet, Varennes, J3X 1S2, Quebec, Canada

    Andrea A. Greschner

  3. School of Physical Sciences, Ingram Building, University of Kent, Canterbury, CT2 7NH, Kent, UK

    Christopher J. Serpell

  4. Department of Chemistry, Queen's University, Chernoff Hall, 90 Bader Lane, Kingston, K7L 3N6, Ontario, Canada

    Anne Petitjean

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Contributions

H.F.S. and F.A. conceived the study. N.A., F.A. and H.F.S. designed the experiments. N.A. performed the experimental studies with assistance from A.A.G. (DNA synthesis), C.J.S. (adenosine/CA crystal growth and X-ray analysis), A.P. (VPO) and V.T. (synthesis of TIPDS-dA and hex-CA). N.A. and H.F.S analysed the data and wrote the manuscript.

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Correspondence to Hanadi F. Sleiman.

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Avakyan, N., Greschner, A., Aldaye, F. et al. Reprogramming the assembly of unmodified DNA with a small molecule. Nature Chem 8, 368–376 (2016). https://doi.org/10.1038/nchem.2451

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