Metallation-Induced Heterogeneous Dynamics of DNA Revealed by Single-Molecule FRET |
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Authors: | Raul Berrocal-Martin Dr Carlos Sanchez-Cano Dr Cookson K C Chiu Dr Russell J Needham Prof Peter J Sadler Dr Steven W Magennis |
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Institution: | 1. School of Chemistry, University of Glasgow, University Avenue, Glasgow, G12 8QQ UK;2. Department of Chemistry, University of Warwick, Gibbet Hill, Coventry, CV4 7AL UK |
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Abstract: | The metallation of nucleic acids is key to wide-ranging applications, from anticancer medicine to nanomaterials, yet there is a lack of understanding of the molecular-level effects of metallation. Here, we apply single-molecule fluorescence methods to study the reaction of an organo-osmium anticancer complex and DNA. Individual metallated DNA hairpins are characterised using Förster resonance energy transfer (FRET). Although ensemble measurements suggest a simple two-state system, single-molecule experiments reveal an underlying heterogeneity in the oligonucleotide dynamics, attributable to different degrees of metallation of the GC-rich hairpin stem. Metallated hairpins display fast two-state transitions with a two-fold increase in the opening rate to ≈2 s?1, relative to the unmodified hairpin, and relatively static conformations with long-lived open (and closed) states of 5 to ≥50 s. These studies show that a single-molecule approach can provide new insight into metallation-induced changes in DNA structure and dynamics. |
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Keywords: | DNA FRET metallodrugs organo-osmium complexes single-molecule studies |
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