Conformational Analysis of Endothelin-1 Analogs with Indolizidinone Amino Acids Incorporated at the C-Terminus
Bibliographic record
Abstract
In light of the fact that a beta-turn conformation at the C-terminus of endothelin-1 (ET-1) could be responsible for activity at the ET(B) receptor, the incorporation of (3S, 6S, 9S)-2-oxo-3-amino-1-azabicyclo[4.3.0]nonane-9-carboxylic acid (IAA) should provide an elegant method to establish whether a formyl group on Trp21 plays a role in stabilizing a beta-turn. Eight linear ET-1 analogs, four formylated and four nonformylated, ET-1-(Leu17-Asp18-IAA-Trp21); ET-1-(Leu17-IAA-Ile20-Trp21); ET-1-(Leu17-Asp18-Pro19-Ile20-Trp21) and ET-1-(Leu17-Asp 8-Ile19-Pro20-Trp21) have been analyzed by high-resolution nuclear magnetic resonance (NMR) spectroscopy and molecular modeling. Two-dimensional double quantum filtered correlation spectroscopy (DQFCOSY), total correlation spectroscopy (TOCSY) and nuclear Overhausen enhancement spectroscopy (NOESY) were resolved and analyzed for each molecule. Interspatial distance constraints were derived from the intensity of the NOESY connectivities, The formation of hydrogen bonding was monitored from the temperature-dependence of the NH chemical shifts. Molecular models calculated by means of distance geometry, simulated annealing and energy minimization, suggested a global elongated structure for the formylated analogs and a folded arrangement for the nonformylated derivatives, but no hydrogen bonding was detected at the C-terminus of ET-1 analogs.
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How this classification was reachedexpand
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 teacher head, 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".