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Solution structure of a DNA duplex containing a replicable difluorotoluene–adenine pair

Nature Structural Biology volume 5, pages 954–959 (1998)Cite this article

Abstract

A nonpolar aromatic nucleoside derivative based on 2,4-difluorotoluene (F), a non-hydrogen bonding shape analog of thymidine, was recently shown to be replicated against adenine with high efficiency and fidelity. This led to the suggestion that geometric matching, potentially even in the absence of hydrogen bonding between bases in a pair, may be sufficient to direct nucleotide selection during replication. We have examined the solution structure of the F–A pair in the context of a 12 base pair DNA duplex. We find that, despite the destabilization caused by this analog, the F–A pair very closely resembles that of a T·A pair in the same context. This lends support to the importance of shape matching in replication.

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Figure 1: a, Schematic model of a 2,4-difluorotoluene adenine pair.
Figure 2: a, Thermal denaturation curves of F6–A19 duplex (red) and a control duplex (blue) containing thymine in place of 2,4-difluorotoluene.
Figure 3: a, Superposition of 12 randomly selected final structures, six of which started from B-form DNA and six from A-form DNA.

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Acknowledgements

We thank the NIH for support. We thank M. Fountain for many helpful discussions.

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Authors and Affiliations

  1. Department of Chemistry, University of Rochester, Rochester, 14627, New York, USA

    Kevin M. Guckian, Thomas R. Krugh & Eric T. Kool

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  1. Kevin M. Guckian
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  2. Thomas R. Krugh
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  3. Eric T. Kool
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Correspondence to Thomas R. Krugh or Eric T. Kool.

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Guckian, K., Krugh, T. & Kool, E. Solution structure of a DNA duplex containing a replicable difluorotoluene–adenine pair. Nat Struct Mol Biol 5, 954–959 (1998). https://doi.org/10.1038/2930

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