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Published on: January 20, 2016
Long-Range Allosteric Modulation of DNA Duplex Dynamics Induced by Pyrrole-Imidazole Polyamide Binding
Sophie E T Kendall-Price1, Ryan J O Nichol2, Andrea Taladriz-Sender2
1Department of Chemistry and York Biomedical Research Institute, University of York, Heslington, York YO10 5DD, U.K.
None:
The allosteric modulation of the structural dynamics of double-stranded DNA (dsDNA) duplexes as a function of distance from the site of a minor groove binding ligand is reported. Time-resolved temperature-jump infrared spectroscopy is used to interrogate the impact of binding a pyrrole-imidazole polyamide to dsDNA sequences 8-14 base-pairs in length. Our results demonstrate that the binding of the hairpin polyamide to its target site (5'-WWGTACW-3'; W = A/T) causes a marked suppression of structural dynamics, such as end fraying, with suppression observed in both the 3' and 5' directions. Quantitative analysis of end fraying suppression reveals a propagation length for dynamic modulation of 30 base-pairs. Identifying the structural impact of minor groove binding to dsDNA sequences furthers our understanding of the influence of dsDNA recognition and informs the design of next-generation synthetic transcription factors.
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