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A poly(thymine)–melamine duplex for the assembly of DNA nanomaterials

Nature Materials volume 19, pages 1012–1018 (2020)Cite this article

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Abstract

The diversity of DNA duplex structures is limited by a binary pair of hydrogen-bonded motifs. Here we show that poly(thymine) self-associates into antiparallel, right-handed duplexes in the presence of melamine, a small molecule that presents a triplicate set of the hydrogen-bonding face of adenine. X-ray crystallography shows that in the complex two poly(thymine) strands wrap around a helical column of melamine, which hydrogen bonds to thymine residues on two of its three faces. The mechanical strength of the thymine–melamine–thymine triplet surpasses that of adenine–thymine base pairs, which enables a sensitive detection of melamine at 3 pM. The poly(thymine)–melamine duplex is orthogonal to native DNA base pairing and can undergo strand displacement without the need for overhangs. Its incorporation into two-dimensional grids and hybrid DNA–small-molecule polymers highlights the poly(thymine)–melamine duplex as an additional tool for DNA nanotechnology.

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Fig. 1: Potential hydrogen-bonding complexes between MA and T.
Fig. 2: Analysis of the poly(T)–MA interaction by native PAGE.
Fig. 3: Crystallographic study of the T6–MA complex.
Fig. 4: Mechanical properties of poly(T)–MA duplexes.
Fig. 5: Mechanochemical sensing of MA using poly(T) templates.
Fig. 6: Applying poly(T)–MA to programme the self-assembly of DNA nanostructures.

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Data availability

Crystallography data (Fig. 3) are available from the Protein Data Bank (https://www.rcsb.org/) with access code 6WK7. The source data related to Figs. 4 and 5 are available upon request from the corresponding authors. All other data in the paper are provided as Source data.

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Acknowledgements

This work was financial support by ONR (N00014-15-1-2707) and NSFC (21974111) to C.M., National Science Foundation (CBET-1904921) and National Institutes of Health (NIH 1R01CA236350) (in part) to H.M., the Natural Sciences and Engineering Research Council (NSERC) of Canada and the Canada Research Chairs Program to H.F.S. and F.J.R., and the Government of Canada for a Banting Fellowship to F.J.R.

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Author notes

  1. These authors contributed equally: Qian Li, Jiemin Zhao, Longfei Liu, Sagun Jonchhe, Felix J. Rizzuto.

Authors and Affiliations

  1. Department of Chemistry, Purdue University, West Lafayette, IN, USA

    Qian Li, Jiemin Zhao, Longfei Liu, Sansen Wei & Chengde Mao

  2. Department of Chemistry and Biochemistry, Kent State University, Kent, OH, USA

    Sagun Jonchhe, Shankar Mandal & Hanbin Mao

  3. Department of Chemistry, McGill University, Montréal, Québec, Canada

    Felix J. Rizzuto & Hanadi F. Sleiman

  4. Biological Science Research Center, Southwest University, Chongqing, China

    Huawei He

  5. Advanced Materials and Liquid Crystal Institute, Kent State University, Kent, OH, USA

    Hanbin Mao

  6. College of Pharmaceutical Sciences, Southwest University, Chongqing, China

    Chengde Mao

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Contributions

H.F.S., H.M. and C.M supervised the project. Q.L. and S.W. conducted PAGE analyses. J.Z. and H.H. conducted crystallographic analysis. L.L. conducted AFM imaging. S.J. and S.M. conducted mechanical measurements. Q.L. and F.J.R. conducted CD, thermal denaturation and assembly mechanism experiments. All the authors contributed to the data analysis and the writing of the manuscript.

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Correspondence to Hanadi F. Sleiman, Hanbin Mao or Chengde Mao.

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Supplementary Information

Supplementary Figs. 1–26 and Tables 1–3.

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Source data

Source Data Fig. 3

Source data for crystallography.

Source Data Fig. 4

Source data for mechanical force spectroscopy.

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Source data for mechanical force spectroscopy.

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Li, Q., Zhao, J., Liu, L. et al. A poly(thymine)–melamine duplex for the assembly of DNA nanomaterials. Nat. Mater. 19, 1012–1018 (2020). https://doi.org/10.1038/s41563-020-0728-2

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