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Record W2021137846 · doi:10.1021/ja709975z

Direct NMR Detection of Alkali Metal Ions Bound to G-Quadruplex DNA

2008· article· en· W2021137846 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueJournal of the American Chemical Society · 2008
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA and Nucleic Acid Chemistry
Canadian institutionsQueen's University
Fundersnot available
KeywordsChemistryAlkali metalG-quadruplexThymineIonMoleculeMetal ions in aqueous solutionCrystallographySolid-state nuclear magnetic resonanceDNANuclear magnetic resonanceOrganic chemistry

Abstract

fetched live from OpenAlex

We describe a general multinuclear (1H, 23Na, 87Rb) NMR approach for direct detection of alkali metal ions bound to G-quadruplex DNA. This study is motivated by our recent discovery that alkali metal ions (Na+, K+, Rb+) tightly bound to G-quadruplex DNA are actually "NMR visible" in solution (Wong, A.; Ida, R.; Wu, G. Biochem. Biophys. Res. Commun. 2005, 337, 363). Here solution and solid-state NMR methods are developed for studying ion binding to the classic G-quadruplex structures formed by three DNA oligomers: d(TG4T), d(G4T3G4), and d(G4T4G4). The present study yields the following major findings. (1) Alkali metal ions tightly bound to G-quadruplex DNA can be directly observed by NMR in solution. (2) Competitive ion binding to the G-quadruplex channel site can be directly monitored by simultaneous NMR detection of the two competing ions. (3) Na+ ions are found to locate in the diagonal T4 loop region of the G-quadruplex formed by two strands of d(G4T4G4). This is the first time that direct NMR evidence has been found for alkali metal ion binding to the diagonal T4 loop in solution. We propose that the loop Na+ ion is located above the terminal G-quartet, coordinating to four guanine O6 atoms from the terminal G-quartet and one O2 atom from a loop thymine base and one water molecule. This Na+ ion coordination is supported by quantum chemical calculations on 23Na chemical shifts. Variable-temperature 23Na NMR results have revealed that the channel and loop Na+ ions in d(G4T4G4) exhibit very different ion mobilities. The loop Na+ ions have a residence lifetime of 220 micros at 15 degrees C, whereas the residence lifetime of Na+ ions residing inside the G-quadruplex channel is 2 orders of magnitude longer. (4) We have found direct 23Na NMR evidence that mixed K+ and Na+ ions occupy the d(G4T4G4) G-quadruplex channel when both Na+ and K+ ions are present in solution. (5) The high spectral resolution observed in this study is unprecedented in solution 23Na NMR studies of biological macromolecules. Our results strongly suggest that multinuclear NMR is a viable technique for studying ion binding to G-quadruplex DNA.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.343

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.238
Teacher spread0.230 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it