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

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.

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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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 Figs. 1–26 and Tables 1–3.

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Source Data Fig. 3

Source data for crystallography.

Source Data Fig. 4

Source data for mechanical force spectroscopy.

Source Data Fig. 5

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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