Bioimaging and Biodistribution of the Metal‐Ion‐Controlled Self‐Assembly of PYY<sub>3–36</sub> Studied by SPECT/CT
Bibliographic record
Abstract
Abstract The controlled self‐assembly of peptide‐ and protein‐based pharmaceuticals is of central importance for their mode of action and tuning of their properties. Peptide YY 3–36 (PYY 3–36 ) is a 36‐residue peptide hormone that reduces food intake when peripherally administered. Herein, we describe the synthesis of a PYY 3–36 analogue functionalized with a metal‐ion‐binding 2,2’‐bipyridine ligand that enables self‐assembly through metal complexation. Upon addition of Cu II , the bipyridine‐modified PYY 3–36 peptide binds stoichiometric quantities of metal ions in solution and contributes to the organization of higher‐order assemblies. In this study, we aimed to explore the size effect of the self‐assembly in vivo by using non‐invasive quantitative single‐photon emission computed tomography/computed tomography (SPECT/CT) imaging. For this purpose, bipyridine‐modified PYY 3–36 was radiolabeled with a chelator holding 111 In III , followed by the addition of Cu II to the bipyridine ligand. SPECT/CT imaging and biodistribution studies showed fast renal clearance and accumulation in the kidney cortex. The radiolabeled bipyridyl‐PYY 3–36 conjugates with and without Cu II presented a slightly slower excretion 1 h post injection compared to the unmodified‐PYY 3–36 , thus demonstrating that higher self‐assemblies of the peptide might have an effect on the pharmacokinetics.
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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 | 0.000 |
| 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".