Cell-penetrating peptides and proteins: new inhibitors of allergic airways diseaseThis review is an invited paper from 2007 ICRH Leadership in Science: a Forum for Trainees and New Investigators.
Bibliographic record
Abstract
Cell-penetrating peptides (CPPs) or protein transduction domains (PTDs) are peptides that have the ability to efficiently traverse cellular membranes, either alone or in association with molecular cargo. Several naturally occurring PTDs, including those from HIV TAT and Drosophila antennapedia, have this unique activity. Synthetic CPPs, such as polyarginine, also have the ability to enter cells and transport a variety of cargo. While the precise mechanism(s) of cellular entry for individual CPPs may vary, it is likely that uptake is mediated, at least in part, through endocytosis. Moreover, biological activity of cell-penetrating peptides and proteins has been clearly demonstrated in a number of in vitro and in vivo studies. Recently, cell-penetrating proteins targeting the Ras GTPase and the phospholipid kinase PI3K (phosphoinositide 3-kinase) have been shown to inhibit eosinophil trafficking and survival in vitro. These proteins, as well as CPPs targeting the STAT-6 transcription factor or the T-cell costimulatory molecule CTLA-4 (cytotoxic T lymphocyte-associated antigen-4), have also been tested in animal models of asthma. Data from several groups, including ours, indicate that these molecules inhibit airway eosinophilic inflammation, airway hyperresponsiveness (AHR), and mucus production in experimental allergic airways disease. Thus, CPPs targeting these and other signaling molecules may also effectively inhibit allergic airways disease in humans.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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 source (direct Gemma or distilled Codex), 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".