Synthesis, Characterisation, and In Vitro Evaluation of Pro<sup>2</sup>‐Ile<sup>3</sup>‐<i>S</i>‐Deoxo‐Amaninamide and Pro<sup>2</sup>‐<scp>D</scp>‐<i>allo</i>‐Ile<sup>3</sup>‐<i>S</i>‐Deoxo‐Amaninamide: Implications for Structure–Activity Relationships in Amanitin Conformation and Toxicity
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
The amatoxins are a family of toxic bicyclic peptides that inhibit RNA polymerase II. Herein we discuss an improved synthesis of these compounds from easily obtainable amino acids by means of a solid-phase methodology. Interestingly, we obtained two products of the same mass following our final macrocyclisation, relating to a similar distribution of products described in some previous reports. One of these products was the desired amatoxin; Pro(2)-Ile(3)-S-deoxo-amaninamide 1 b. The other compound, after thorough investigation, was confirmed to be the epimer Pro(2)-D-allo-Ile(3)-S-deoxo-amaninamide 1 a, not an atropisomer structure as previously suggested in syntheses of related amanitin analogues. Crystallographic data of 1 a confirms the presence of a betaII-turn, rather than a betaI-turn common to the natural toxin and 1 b. This difference explains the large variation in CD spectra, although it seems to have relatively little effect on the bioactivity in vitro. These data provide new insights into the bicyclic amatoxin 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 | 0.005 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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