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Autonomous multistep organic synthesis in a single isothermal solution mediated by a DNA walker


Multistep synthesis in the laboratory typically requires numerous reaction vessels, each containing a different set of reactants. In contrast, cells are capable of performing highly efficient and selective multistep biosynthesis under mild conditions with all reactants simultaneously present in solution1,2,3,4. If the latter approach could be applied in the laboratory, it could improve the ease, speed and efficiency of multistep reaction sequences. Here, we show that a DNA mechanical device—a DNA walker moving along a DNA track—can be used to perform a series of amine acylation reactions in a single solution without any external intervention. The products of these reactions are programmed by the sequence of the DNA track, but they are not related to the structure of DNA. Moreover, they are formed with speeds and overall yields that are significantly greater than those previously achieved by multistep DNA-templated small-molecule synthesis.

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Figure 1: Overview of the DNAsome system.
Figure 2: Analysis of reaction products generated by the DNAsome system.
Figure 3: Mass spectroscopy analysis of reactions identical to the one shown in Fig. 2a, but using different DNA tracks or with no DNA track.


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This work was supported by the Howard Hughes Medical Institute and National Institutes of Health/National Institute of General Medical Sciences (R01GM065865). The authors thank C. Dumelin and Y. Chen for insightful discussions and experimental assistance. The authors are grateful to Y. Shen for assistance with mass spectrometry.

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Y.H. and D.L. conceived and designed the project, analysed the data and wrote the manuscript. Y.H. performed the experiments.

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Correspondence to David R. Liu.

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Competing interests

D.L. is a consultant for Ensemble Discovery, a company that uses DNA-templated synthesis for industrial applications.

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He, Y., Liu, D. Autonomous multistep organic synthesis in a single isothermal solution mediated by a DNA walker. Nature Nanotech 5, 778–782 (2010).

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