Mechanistic Studies on the Application of DNA Aptamers as Inhibitors of 2-Oxoglutarate-Dependent Oxygenases
Bibliographic record
Abstract
The Escherichia coli (E. coli) AlkB protein and its functional human homologues belong to a subfamily of 2-oxoglutarate (2OG) dependent oxygenases (2OG oxygenases for simplicity) that enable the repair of cytotoxic methylation damage in nucleic acids and that catalyze t-RNA oxidations. DNA alkylation is a major mechanism of action for cytotoxic anticancer drugs. Thus, the inhibition of oxidative demethylation, catalyzed by these enzymes, has the potential to improve the efficacy of chemotherapies. Here we report that oligonucleotide aptamers constitute a new class of potent inhibitors of 2OG oxygenases. DNA aptamers can selectively bind to AlkB, with nanomolar affinity, and efficiently inhibit catalysis. The mechanism of inhibition was studied by capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection. Inhibition constants of the aptamers were determined and shown to correlate well with K(d) values. The results of kinetic analyses imply that the aptamers bind AlkB away from the active site. Our findings should stimulate the development of oligonucleotide aptamers for human homologues of AlkB and further their study as potential enhancers of chemotherapy efficiency.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".