Long-Range Allosteric Modulation of DNA Duplex Dynamics Induced by Pyrrole-Imidazole Polyamide Binding.

ABSTRACT: 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.

SUBMITTER: Kendall-Price SET 

PROVIDER: S-EPMC12337142 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature