An Analysis of the Affinity and Stability of Base Pair Modifications of the Glucose-Binding and Cocaine-Binding Aptamers
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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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 | 0.001 |
| 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 | 0.001 |
| 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 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".