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Solution structure of a DNA double helix with consecutive metal-mediated base pairs

Nature Chemistry volume 2, pages 229–234 (2010)Cite this article

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Abstract

Metal-mediated base pairs represent a powerful tool for the site-specific functionalization of nucleic acids with metal ions. The development of applications of the metal-modified nucleic acids will depend on the availability of structural information on these double helices. We present here the NMR solution structure of a self-complementary DNA oligonucleotide with three consecutive imidazole nucleotides in its centre. In the absence of transition-metal ions, a hairpin structure is adopted with the artificial nucleotides forming the loop. In the presence of Ag(i) ions, a duplex comprising three imidazole–Ag+–imidazole base pairs is formed. Direct proof for the formation of metal-mediated base pairs was obtained from 1J(15N,107/109Ag) couplings upon incorporation of 15N-labelled imidazole. The duplex adopts a B-type conformation with only minor deviations in the region of the artificial bases. This work represents the first structural characterization of a metal-modified nucleic acid with a continuous stretch of metal-mediated base pairs.

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Figure 1: Description of the oligonucleotide system under investigation.
Figure 2: Comparison of sections of the [1H,1H]-NOESY and [1H,15N]-HSQC spectra of the hairpin (left) and metallated helix (right).
Figure 3: Direct evidence for the formation of imidazole–Ag+–imidazole base pairs.
Figure 4: Lowest-energy structure of the duplex containing the Ag+-mediated imidazole base pairs in its centre.
Figure 5: According to the base-pair parameters, the Ag(i)-containing double helix adopts a regular B-DNA structure with only slight deviations (see also Supplementary Fig. S3).

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Acknowledgements

Financial support by the European ERAnet-Chemistry, the Swiss National Science Foundation (20EC21-112708 and 200021-124834 to R.K.O.S.), the Swiss State Secretariat for Education and Research (R.K.O.S.), the Deutsche Forschungsgemeinschaft (MU1750/1-3 and MU1750/2-1 to JM), COST D39 and the Fonds der Chemischen Industrie (J.M.) is gratefully acknowledged. We also thank T. van der Wijst for providing us with the partial charges of protonated and unprotonated 1-methylimidazole, as well as R. Micura and K. Breuker, University of Innsbruck, for recording mass spectra.

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Authors and Affiliations

  1. Institute of Inorganic Chemistry, University of Zürich, Winterthurerstr. 190, Zürich, 8057, Switzerland

    Silke Johannsen & Roland K. O. Sigel

  2. Westfälische Wilhelms-Universität Münster, Institut für Anorganische und Analytische Chemie, Corrensstr. 28/30, Münster, 48149, Germany

    Nicole Megger, Dominik Böhme & Jens Müller

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  1. Silke Johannsen
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Contributions

J.M. and R.K.O.S. designed research, N.M. and D.B. performed syntheses, S.J. performed the NMR experiments and structure calculations, S.J. and R.K.O.S. analysed data, and J.M., R.K.O.S., S.J. and N.M. wrote the manuscript.

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Correspondence to Roland K. O. Sigel or Jens Müller.

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Johannsen, S., Megger, N., Böhme, D. et al. Solution structure of a DNA double helix with consecutive metal-mediated base pairs. Nature Chem 2, 229–234 (2010). https://doi.org/10.1038/nchem.512

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