Engineering Peptide Modulators for T-Cell Migration by Structural Scaffold Matching
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide Lymphocyte migration plays a crucial role in the progression of autoimmune and inflammatory diseases, and the inhibition of autoreactive immune cells is an attractive therapeutic strategy. Pepitem is an endogenous modulator of lymphocyte migration. In this study, we implemented a structural scaffold matching approach to engineer of stabilized pepitem-based probes. Prioritizing the native helix–loop–helix structure of pepitem, protein structure databases were mined to identify the structurally closest peptide scaffold. Leveraging this strategy, we developed VhTI-pep 2, inhibiting CD3 + T-lymphocyte migration in vitro with a comparable potency (EC 50 = 10.6 ± 16.5 nM) to pepitem (EC 50 = 6.0 ± 6.4 nM). Its potency was further extended to T-cell subsets derived from multiple sclerosis patients and highly disease-driving memory and Th1 cell populations. Our approach will guide the design of stabilized peptide probes and future therapeutics, overcoming the challenges associated with flexible and linear peptides.
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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".