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Enzyme-free translation of DNA into sequence-defined synthetic polymers structurally unrelated to nucleic acids

Nature Chemistry volume 5, pages 282–292 (2013)Cite this article

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Abstract

The translation of DNA sequences into corresponding biopolymers enables the production, function and evolution of the macromolecules of life. In contrast, methods to generate sequence-defined synthetic polymers with similar levels of control have remained elusive. Here, we report the development of a DNA-templated translation system that enables the enzyme-free translation of DNA templates into sequence-defined synthetic polymers that have no necessary structural relationship with nucleic acids. We demonstrate the efficiency, sequence-specificity and generality of this translation system by oligomerizing building blocks including polyethylene glycol, α-(D)-peptides, and β-peptides in a DNA-programmed manner. Sequence-defined synthetic polymers with molecular weights of 26 kDa containing 16 consecutively coupled building blocks and 90 densely functionalized β-amino acid residues were translated from DNA templates using this strategy. We integrated the DNA-templated translation system developed here into a complete cycle of translation, coding sequence replication, template regeneration and re-translation suitable for the iterated in vitro selection of functional sequence-defined synthetic polymers unrelated in structure to nucleic acids.

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Figure 1: Natural and laboratory translation of nucleic acids into non-nucleic acid polymers.
Figure 2: Evaluation of building-block coupling chemistries.
Figure 3: Identification and analysis of full-length translation products.
Figure 4: Sequence specificity of translation using templates containing mixtures of codons.
Figure 5: Translation of DNA sequences into longer polymers and polymers of different backbone structures.
Figure 6: A complete cycle of translation, PCR amplification, strand separation and re-translation.

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Acknowledgements

This work was supported by the Howard Hughes Medical Institute and the NIH/NIGMS (R01GM065865). J.N. was partially supported by an Eli Lilly Organic Chemistry Graduate Fellowship. R.H. was supported by a postdoctoral fellowship from Canada's National Science and Engineering Council (NSERC). The authors are grateful to J. Heemstra, Y. Brudno, C. Dumelin, Y. Lu and S. Trauger for helpful discussions.

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  1. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, 02138, Massachusetts, USA

    Jia Niu, Ryan Hili & David R. Liu

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J.N., R.H. and D.R.L. designed the research, analysed the data and co-wrote the manuscript. J.N. performed the experiments.

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Correspondence to David R. Liu.

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Niu, J., Hili, R. & Liu, D. Enzyme-free translation of DNA into sequence-defined synthetic polymers structurally unrelated to nucleic acids. Nature Chem 5, 282–292 (2013). https://doi.org/10.1038/nchem.1577

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