Insights into the Molecular Determinants Involved in Urocontrin and Urocontrin A Action
Bibliographic record
Abstract
In the past few years, we have identified two allosteric modulators of the urotensinergic system with probe-dependent action, termed Urocontrin (UC) and Urocontrin A (UCA). Such action is atypical and important since it will allow us to understand the specific function of the functionally selective cognate ligands of this system, namely urotensin II and urotensin II-related peptide. Delineating the molecular determinants involved in this particular behavior would represent an important step toward designing small molecules suitable for pharmacologic and/or therapeutic intervention. Hence, we undertook an exploratory research by replacing the Trp4 residue of URP with several para-substituted phenylalanine amino acids in order to get a grasp on the required nature, distance, and orientation of the side chain of this residue for allosteric modulatory action. We found that the position of the second aromatic group is crucial, and we identified two new allosteric modulators: [Trip4]URP and [Phe(pPy-4)4]URP with probe-dependent action.
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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 | 0.000 | 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) | 0.000 | 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".