Nucleic Acid FRET Sensing of Hydrogen Peroxide in Live Cells Using a Boronic Acid Nucleobase Surrogate
Why this work is in the frame
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Bibliographic record
Abstract
For activity-based sensing, where probes detect biological analytes through chemical reactivity, nucleic acid (NA) scaffolds represent an attractive platform to enhance biocompatibility and permit ratiometric analyte detection through the precise control of distance and orientation of donor/acceptor probes within the duplex framework for a turn-on FRET response. Herein, we present the first all-in-one NA FRET sensor (KR28) that is activated by H 2 O 2 as a molecular trigger in human serum and in the nucleus of live cells. The 28-mer 2′-OMe-XNA hairpin (HP) KR28 features a boronic acid nucleobase surrogate (BA6HI) that serves as the H 2 O 2 sensing element and is embedded into KR28 using an on-strand Aldol condensation approach. ipso -Hydroxylation of the BA6HI surrogate mediated by H 2 O 2 furnishes an emissive phenolic product (PhOH6HI, λ ex /λ em = 390/490 nm) that serves as the FRET donor to a thiophene surrogate acceptor (Th6HI, λ ex /λ em = 530/580 nm) for a FRET efficiency ∼ 95%. The BA6HI-modified NA scaffolds can detect H 2 O 2 in the low nM regime and localize in the nucleus of live cells for nuclear H 2 O 2 FRET detection. Our work expands the function of NA scaffolds beyond their use as molecular recognition elements through noncovalent affinity interactions and demonstrates their potential to serve as activity-based sensors of ROS to probe the relationships between nuclear oxidative stress and disease states.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it