Novel Disulfide-Containing Linkages of Pyrimidine Nucleobases to Solid Supports: A Versatile Platform for Oligonucleotide Conjugation
Bibliographic record
Abstract
Conjugation of ligands to oligonucleotides is a prominent strategy to enhance (bio)properties of nucleic acids such as cellular uptake/delivery, bioavailability, detection/tracking, and more. Here, we report a simple, cost-effective, and streamlined methodology for the incorporation of various conjugation handles into DNA and RNA. Pyrimidine nucleosides are linked to the solid support via a disulfide-containing linker covalently attached through the nucleobase, removing the typical sugar point-of-attachment requirement. We showcase a conjugation strategy in which nucleic acid strands can be permanently tagged with a ligand (via an azido group) and reversibly conjugated to another (via the linker containing a disulfide and primary amino group). Freed thiols can undergo further conjugation in certain constructs. Ultimately, our conjugation handles containing various orthogonal functional groups (e.g., azido, amino, and disulfide functional groups) will find applications in biotechnology and chemical biology.
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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 | 0.001 |
| 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) | 0.001 | 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".