Diversity-oriented solid-phase synthesis and biological evaluation of oligonucleotide hairpins as HIV-1 RT RNase H inhibitors
Bibliographic record
Abstract
The inhibitory potencies of several hairpins comprising DNA, RNA and 2',5'-linked RNA segments were assessed against the RNase H activity of the human immunodeficiency virus reverse transcriptase (HIV-1 RT), an indispensable enzyme for HIV genomic replication. The hairpin library was constructed via diversity-oriented nucleic-acid synthesis (DONAS), an approach inspired from traditional split-pool synthesis. DONAS provided access to an array of oligonucleotide hairpins possessing distinct conformational, structural and biological properties. The inhibitory potency of these compounds was highly specific towards HIV-1 RT RNase H and strongly depended on the structure of both the stem and tetraloop. Hairpins that have an overall A-type geometry are better inhibitors of RNase H activity than hairpins with 'intermediate' or B-type conformations, although interestingly, the inhibitory activity is quite sensitive to the nucleotide sequence in both the stem and loop regions of the hairpin. The most potent hairpins bear a 3',5'-linked rather than 2',5'-linked RNA loop, but the latter is necessary for activity of hairpins consisting of DNA stems. Inhibitory activity was essentially independent of hairpin thermal stability. The potent hairpins also demonstrated high nuclease resistance in biological media, particularly those bearing a 2',5'-linked tetraloop. These studies collectively bring into light a new class of nucleic acid aptamers that act exclusively upon the retroviral RNase H domain in vitro, and thus represent novel lead compounds for the development of specific and potent HIV-1 RT inhibitors.
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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 | 0.000 | 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 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".