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Metallation‐Induced Heterogeneous Dynamics of DNA Revealed by Single‐Molecule FRET
Author(s) -
BerrocalMartin Raul,
SanchezCano Carlos,
Chiu Cookson K. C.,
Needham Russell J.,
Sadler Peter J.,
Magennis Steven W.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202000458
Subject(s) - förster resonance energy transfer , chemistry , single molecule fret , oligonucleotide , dna , single molecule experiment , osmium , molecule , fluorescence , nucleic acid , molecular dynamics , biophysics , computational chemistry , biochemistry , biology , ruthenium , physics , organic chemistry , quantum mechanics , catalysis
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.