Fluorescent Properties and Conformational Preferences of C-Linked Phenolic-DNA Adducts
Bibliographic record
Abstract
Phenolic toxins and mutagenic diazoquinones generate C-linked adducts at the C8 site of 2'-deoxyguanosine (dG) through the intermediacy of radical species. We have previously reported the site-specific incorporation of these adducts into oligonucleotides using a postsynthetic palladium-catalyzed cross-coupling strategy [Omumi (2011 ) J. Am. Chem. Soc. 133 , 42 - 50 ]. We report here the structural impact of these lesions within two decanucleotide sequences containing either 5'- and 3'-flanking pyrimidines or purines. In the complementary strands, the base opposite (N) the C-linked adduct was varied to determine the possibility of mismatch stabilization by the modified nucleobases. The resulting adducted duplex structures were characterized using UV thermal denaturation studies, circular dichroism, fluorescence spectroscopy, and molecular dynamics (MD) simulations. The experimental data showed the C-linked adducts to destabilize the duplex when base paired with its normal partner C but to increase duplex stability within a G:G mismatch. The stabilization within the G:G mismatch was sequence dependent, with flanking purine bases playing a key role in the stabilizing influence of the adduct. MD simulations showed no large structural changes to the B form double helix, regardless of the (anti/syn) adduct preference. Consideration of H-bonding and stacking interactions derived from the MD simulations together with the thermal melting data and changes in fluorescent emission of the adducts upon hybridization to the complementary strands implied that the C-linked phenolic adducts preferentially adopt the syn-conformation within both duplexes regardless of the opposite base N. Given that biological outcome in terms of mutagenicity appears to be strongly correlated to the conformational preference of the corresponding N-linked C8-dG adducts, the potential biological implications of phenolic C-linked adducts are discussed.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 | 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".