Synthesis and structural studies of nucleic acids
Bibliographic record
Abstract
The first project focused on the synthesis of 4-15N-2′-deoxycytidine as a tool to study the B- to Z-DNA transition using 15N NMR. This study investigated alternative methods for synthesizing 15N enriched 2′-deoxycytidine at the 4-NH2 position. As a model study, ammonium chloride was used as the 15N source to synthesize 5-methyl-2′-deoxycytidine from thymidine. This chemistry was successfully applied to the synthesis 4-15N-2′-deoxycytidine from 2′-deoxyuridine. In addition, the 15N NMR detection limit was also established to determine the feasibility of studying DNA structures using 15N 1D NMR. \nThe second project involved finding ‘difficult sequences’ in solid-phase oligonucleotide synthesis through phosphoramidite chemistry. Using 18-mers as models, all mathematically possible repeating trinucleotides, dinucleotide, and mononucleotide sequences were synthesized, and the overall yields were analyzed by anion exchange high performance liquid chromatography. It was concluded that depurination was a major contributor to decreased yields in purine-rich sequences. In addition, certain dinucleotide-repeat sequences, especially d(CG) and d(GC), were associated with low overall yields for reasons unknown at this time. \nThe last project involved the identification of alternative detritylation composition for industrial solid-phase oligonucleotide synthesis. These compositions include acids, solvents, and carbocation scavengers. The acid currently used in industrial oligonucleotide solid-phase synthesis is dichloroacetic acid, which has a short shelf life and contains impurities that react with the desired reaction product. For solvents used in the detritylation reaction, toluene and dichloromethane are currently used. While dichloromethane is not preferred in industry, toluene has been known to swell the polystyrene solid support creating an issue during detritylation. Furthermore, the use of carbocation scavengers helps to remove the cleaved DMTr+, preventing it from re-protecting 5′-OH. However, some scavengers have been reported as problematic for this purpose. The results of this project provided a potential alternative acid, namely difluoroacetic acid, investigated and explained the reason for the current solvent choice, and studied the feasibility of scavengers used in the literature.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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) | 0.003 | 0.002 |
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".