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Site-specific positioning of dendritic alkyl chains on DNA cages enables their geometry-dependent self-assembly

Nature Chemistry volume 5, pages 868875 (2013) | Download Citation

Abstract

Nature uses a combination of non-covalent interactions to create a hierarchy of complex systems from simple building blocks. One example is the selective association of the hydrophobic side chains that are a strong determinant of protein organization. Here, we report a parallel mode of assembly in DNA nanotechnology. Dendritic alkyl-DNA conjugates are hybridized to the edges of a DNA cube. When four amphiphiles are on one face, the hydrophobic residues of two neighbouring cubes engage in an intermolecular ‘handshake’, resulting in a dimer. When there are eight amphiphiles (four on the top and bottom cube faces, respectively), they engage in an intramolecular ‘handshake’ inside the cube. This forms the first example of a monodisperse micelle within a DNA nanostructure that encapsulates small molecules and releases them by DNA recognition. Creating a three-dimensional pattern of hydrophobic patches, like side chains in proteins, can result in specific, directed association of hydrophobic domains with orthogonal interactions to DNA base-pairing.

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Acknowledgements

The authors acknowledge the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canada Foundation for Innovation (CFI), the Centre for Self-Assembled Chemical Structures (CSACS) and the Canadian Institute for Advanced Research (CIFAR) for financial support. T.G.W.E thanks Canadian Institutes of Health Research (CIHR) for a Drug Development Training Program (DDTP) scholarship. 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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Affiliations

  1. Department of Chemistry and Centre for Self-assembled Chemical Structures, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A2K6, Canada

    • Thomas G. W. Edwardson
    • , Karina M. M. Carneiro
    • , Christopher K. McLaughlin
    • , Christopher J. Serpell
    •  & Hanadi F. Sleiman

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Contributions

H.F.S., T.G.W.E. and K.M.M.C. designed the project. T.G.W.E. primarily contributed to the production of experimental results. T.G.W.E. and K.M.M.C. developed the synthesis of the D-DNA. T.G.W.E. and C.K.M. designed and synthesized the sequences for the DNA scaffold and additional unmodified DNA. All authors discussed the results, commented on the manuscript and have agreed to all the content of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Hanadi F. Sleiman.

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DOI

https://doi.org/10.1038/nchem.1745