AZT Binds RNA at Multiple Sites
Why this work is in the frame
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Bibliographic record
Abstract
Azidothymidine (AZT) is a widely used inhibitor of type I human immunodeficiency virus (HIV) reverse transcriptase that act as a DNA chain terminator. Studies have shown primer unblocking and rescue of DNA synthesis AZT-resistant HIV-1 reverse transcriptase on DNA and RNA templates. Our recent study showed AZT bindings to the G-C, A-T base pairs and the backbone phosphate group of DNA duplex resulting in partial DNA conformational changes. This study was designed to examine the interaction of AZT with RNA in aqueous solution at physiological condition, using different drug/RNA (phosphate) molar ratios of 1/800 to 1/2 and constant RNA concentration of 1.25 or 12.5 mM (phosphate). Capillary electrophoresis, FTIR, and UV-visible difference spectroscopic methods and molecular modeling were used to determine the drug binding sites, binding constants, and the effects of AZT complexation on RNA conformation. Structural analysis showed that AZT binds RNA through G-C and A-U bases with two binding constants of K1=7.3 x 10(5) M(-1) and K2=1.90 x 10(5) M(-1). The drug distributions were 54% with G-C, 36% A-U, and 10% with the backbone phosphate group. RNA remains in A-family structure and drug sugar pucker in the C2'-endo/anti conformation in the AZT-RNA complexes. Molecular modeling studies show hydrogen bondings between RNA and AZT donor groups.
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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 it