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

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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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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