DNA Sequence Recognition of a Cross-Linked Polyamide: CD Studies, Footprinting and Effects on the Activity of DNA Gyrase
Bibliographic record
Abstract
Abstract Using circular dichroism the binding ability of a cross-linked thiazole-lexitropsin, composed of two polyamide strands (with the base binding residues thiazole-imidazole-pyrrole) to a series of dodecamer duplexes containing different central sequences, has been examined. The binding of the dimer with a heptanediyl linker (C7 dimer) was compared with that of the lexitropsin monomer at 200 mM NaCl and 2 M NaCl. The C7 dimer exhibits a clear-cut different binding tendency to various dodecamers at 2 M NaCl indicating that sequence specificity becomes apparent at high salt concentration. The highest binding preference occurs to the dodecamers with the central sequences: AACGTT, AAGTTT and ATCGTA but almost no affinity was observed at 2 M NaCl for AGCGCT, ATCGAT and AAATTT. From the results it appears that the sequence selectivity of the dimer can be ascribed to the side-by-side binding mode of the cross-linked polyamide strands in the minor groove. In contrast no similar variation was found in the binding behavior for the lexitropsin monomer. Modification of the leading residue on the thiazoles of the dimer significantly lowers (or even abolishs) the binding ability, e.g. if the amino group is replaced by formyl or an acetyl residue. Footprinting and melting temperature data are in agreement with the CD results. Comparative in vitro studies on the influence of the lexitropsins on DNA gyrase demonstrate that the dimer has a higher inhibitory potency on the enzymatic activity compared to the monomer in accord with the observed DNA binding differences. A scheme of a possible side- by-side alignment of the C7 dimer in the minor groove is proposed.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".