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A biomolecule-compatible visible-light-induced azide reduction from a DNA-encoded reaction-discovery system

Nature Chemistry volume 3, pages 146–153 (2011)Cite this article

Abstract

Using a system that accelerates the serendipitous discovery of new reactions by evaluating hundreds of DNA-encoded substrate combinations in a single experiment, we explored a broad range of reaction conditions for new bond-forming reactions. We discovered reactivity that led to a biomolecule-compatible, Ru(II)-catalysed azide-reduction reaction induced by visible light. In contrast to current azide-reduction methods, this reaction is highly chemoselective and is compatible with alcohols, phenols, acids, alkenes, alkynes, aldehydes, alkyl halides, alkyl mesylates and disulfides. The remarkable functional group compatibility and mild conditions of the reaction enabled the azide reduction of nucleic acid and oligosaccharide substrates, with no detectable occurrence of side reactions. The reaction was also performed in the presence of a protein enzyme without the loss of enzymatic activity, in contrast to two commonly used azide-reduction methods. The visible-light dependence of this reaction provides a means of photouncaging functional groups, such as amines and carboxylates, on biological macromolecules without using ultraviolet irradiation.

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Figure 1: DNA-encoded reaction-discovery system and validation experiments.
Figure 2: Selection results from four reaction conditions.
Figure 3: Development of the Ru(bpy)3Cl2-mediated azide-reduction reaction induced by visible light.
Figure 4: Compatibility of the azide-reduction reaction with biological molecules.

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Acknowledgements

This work was supported by NIH grant R01GM065865 and the Howard Hughes Medical Institute. We thank Y. Shen and C. Dumelin for MS assistance, and D. Gorin for discussions.

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Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Harvard University, 12 Oxford Street, Cambridge, 02138, MA, USA

    Yiyun Chen, Adam S. Kamlet, Jonathan B. Steinman & David R. Liu

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  1. Yiyun Chen
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  2. Adam S. Kamlet
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  4. David R. Liu
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Contributions

Y.C., A.S.K., J.B.S. and D.R.L. designed the research, analysed the data and co-wrote the manuscript, Y.C., A.S.K. and J.B.S. performed the experiments.

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Correspondence to David R. Liu.

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Chen, Y., Kamlet, A., Steinman, J. et al. A biomolecule-compatible visible-light-induced azide reduction from a DNA-encoded reaction-discovery system. Nature Chem 3, 146–153 (2011). https://doi.org/10.1038/nchem.932

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