An Analysis of the Affinity and Stability of Base Pair Modifications of the Glucose-Binding and Cocaine-Binding Aptamers
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Bibliographic record
Abstract
Aptamers are selected to bind to their ligands, usually with high affinity and selectivity for targets. An aptamer was previously selected to bind glucose with a Kd of 10mM which is physiologically relevant as the blood glucose concentration typically falls between 4-11 mM. NMR spectroscopy is suited to study weak aptamer-ligand interactions and was used to investigate the affinity of sequence modified glucose-binding aptamers to try and determine a sequence with a greater binding affinity. Three of thirteen modifications bound to glucose, the change of a G-T base pair to a G-C base pair (Glumod-7) with a Kd of 2.9mM±0.3mM, the alteration of the terminal triloop from a C-T-C to a G-A-A (Gumod-8) with a Kd of 12mM±3mM, and the truncation by 3 base pairs (Glumod-12) which was too weak to determine a Kd. Glumod-7 was the only sequence which had a comparable Kd and would require further investigation in terms of stability using NMR thermomelts. Cocaine-binding aptamers are intriguing as they are composed of three stems centered around two mismatch A-G base pairs and are very well studied in terms of secondary structure and affinity. The thermostability of cocaine-binding aptamers as a function of number of base pairs in stem one was investigated by DSC. There was a trend observed of increasing in stability from 1 base pair to 6 base pairs with a decrease seen at 7 base pairs. The most thermodynamically stable aptamer was determined to be MN4, a preformed structure.
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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 | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 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