Design, Synthesis, and Evaluation of a New Fluorescent Ligand for the M<sub>2</sub> Muscarinic Acetylcholine Receptor
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide The M 2 muscarinic acetylcholine receptor (M 2 R) is a G protein-coupled receptor involved in regulating cardiovascular functions and mediation of central muscarinic effects, such as movement, temperature control, and antinociceptive responses. Molecular probes targeting this receptor are therefore important in exploring its pathophysiological role at a molecular level. Herein, we report the design, synthesis, and evaluation of a new fluorescent probe for M 2 R based on an anthranilamide ligand. In radioligand binding experiments, the presented Oregon Green 488-labeled conjugate ( 33 ) exhibited high M 2 R affinity ( K i = 2.4 nM), a moderate preference for the M 2 R over the M 4 receptor, and excellent to pronounced M 2 R selectivity compared to the M 1, M 3, and M 5 receptors. The utility of the probe was demonstrated in confocal, two-photon, and stimulated emission depletion nanoscopy (STED) imaging to specifically label the receptors in human embryonic kidney (HEK) 293T cells. These properties suggest that our probe may be utilized in advanced microscopy to study the pharmacology of the M 2 R.
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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) | 0.000 | 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 | 0.000 |
| 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".