biostudies-literatureKendall-Price SETLeverhulme Trust7875-7882https://www.ebi.ac.uk/biostudies/studies/S-EPMC12337142biostudies-literatureUnknown16(31)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.The journal of physical chemistry lettersLong-Range Allosteric Modulation of DNA Duplex Dynamics Induced by Pyrrole-Imidazole Polyamide Binding.PMC12337142RPG-2022-045Phelps RKendall-Price SETMalakar PTaladriz-Sender AGreetham GMHunt NTNichol RJOBurley GAfalseLong-Range Allosteric Modulation of DNA Duplex Dynamics Induced by Pyrrole-Imidazole Polyamide Binding.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.2025-01-01T00:00:00Z2025 Aug2026-04-18T11:17:46.694Z2026-04-07T14:34:51.853ZS-EPMC123371424072054010.1021/acs.jpclett.5c01542