Kendall-Price Sophie E T, Nichol Ryan J O, Taladriz-Sender Andrea, Phelps Ryan, Malakar Partha, Greetham Gregory M, Burley Glenn A, Hunt Neil T
Department of Chemistry and York Biomedical Research Institute, University of York, Heslington, York YO10 5DD, U.K.
Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1BX, U.K.
J Phys Chem Lett. 2025 Aug 7;16(31):7875-7882. doi: 10.1021/acs.jpclett.5c01542. Epub 2025 Jul 28.
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.
报道了双链DNA（dsDNA）双链体结构动力学的变构调节与距小沟结合配体位点的距离之间的函数关系。采用时间分辨温度跳跃红外光谱法研究了吡咯-咪唑聚酰胺与长度为8-14个碱基对的dsDNA序列结合的影响。我们的结果表明，发夹聚酰胺与其靶位点（5'-WWGTACW-3'；W = A/T）的结合会显著抑制结构动力学，如末端解链，在3'和5'方向均观察到抑制作用。对末端解链抑制的定量分析揭示了动态调节的传播长度为30个碱基对。确定小沟与dsDNA序列结合的结构影响，有助于我们进一步理解dsDNA识别的影响，并为下一代合成转录因子的设计提供信息。
