Effect of Linker Length on DNA Duplexes Containing a Mismatched O6-2'-Deoxyguanosine-Alkyl Interstrand Cross-Link
Bibliographic record
Abstract
DNA duplexes containing a directly opposed O(6)- alkyl-2'-deoxyguanosine interstrand cross-link were synthesized to serve as structural mimics of lesions formed by the bifunctional chemotherapeutic alkylating agents busulfan and hepsulfam. One of the key steps to prepare the necessary bis-phosphoramidites involved the Mitsunobu reaction between a diol linking two protected 2'-deoxyguanosine nucleosides at the O(6) position. These bis-phosphoramidites were incorporated into 11-bp DNA duplexes by solid phase synthesis to produce cross-linked DNA probes in high yields. UV thermal denaturation studies revealed that these interstrand cross-linked containing oligonucleotides were stabilized compared to a DNA duplex containing a central 2'-deoxyguanosine mismatch. The duplex containing the four carbon cross-link was stabilized by 10 degrees C relative to the seven carbon linker. Molecular models of these duplexes that were geometry optimized by the AMBER force field suggest that the seven carbon cross-link was less efficiently accommodated in the major groove of the duplex relative to the four carbon linker, accounting for the observed destabilization.
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How this classification was reachedexpand
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".