An approach for the synthesis of duplexes containing <i>N</i><sup>3</sup>T-butyl-<i>N</i><sup>3</sup>T interstrand cross-links via a bisphosphoramidite strategy
Bibliographic record
Abstract
DNA duplexes containing an interstrand cross-link have been synthesized utilizing a bis-3′-O-phosphoramidite deoxythymidine dimer where the N3 atoms are bridged by a butyl linker. With this approach sufficient quantities of high purity cross-linked duplexes are obtained that will enable various biochemical and structural studies to aid in research directed towards understanding the mechanism of interstrand cross-linked DNA repair. This methodology has advantages over a previously reported method to synthesize cross-linked DNA duplexes involving a monophosphoramidite of the same cross-linked thymidine dimer including circumventing the use of costly 5′-O-deoxyphosphoramidites in the assembly of the cross-linked duplex by solid-phase synthesis. This strategy can be employed to produce cross-linked duplexes in which the lesions are engineered to have a directly opposed (1–1) or staggered (1–2 or 2–1) orientations. Biophysical studies of duplexes containing this N3T-butyl-N3T cross-link in staggered 1–2 and 2–1 orientations reveal that both duplexes have a higher Tm than a non-cross-linked duplex suggesting that these linkages do not result in the destabilization of duplex DNA. Circular dichroism spectra of the 1–2 and 2–1 cross-linked duplexes exhibit minor differences from B-form structure, which correlates with molecular modeling studies.Key words: chemically modified oligonucleotides, interstrand cross-link, DNA adduct, DNA repair.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".