Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Nuclear magnetic resonance (NMR) spectroscopy is the only biophysical technique capable of characterizing nucleic acid structures at atomic resolution under near-physiological liquid-state conditions. Still, it is fundamentally limited by intrinsically low sensitivity, particularly when analyzing high-molecular-weight, low-abundance, or polymorphic targets, such as DNAs (DNA). In this study, we demonstrate that hyperpolarized aqueous buffers generated via dissolution dynamic nuclear polarization (dDNP) significantly enhance the 1 H NMR signals of multiple DNA motifs. The resonances of labile imino and amino protons of DNAs dissolved in hyperpolarized buffers are enhanced up to ∼200-fold and ∼370-fold, respectively. These intense signals serve a 2-fold purpose: (i) as structural fingerprints of DNA folding topologies and (ii) they enable the direct observation of low-populated folding intermediates in DNA polymorphs, such as G-quadruplexes (G4) and i-motifs (iM), which remain undetectable by standard methods. Thus, our findings establish hyperpolarized NMR as a high-sensitivity method for probing DNA structures and folding intermediates across a wide range of motifs, opening possible avenues in liquid biopsy applications and cell-free DNA.
DOI: 10.1021/jacs.5c17542
Authors: Milan Zachrdla, Ertan Turhan, Michala Bučková, Robert Hänsel-Hertsch, Lukáš Trantírek, Dennis Kurzbach
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4417122446