Polyethylene Glycol Conjugation at Cys <b>232</b> Prolongs the Half-Life of <b>α</b> 1 Proteinase Inhibitor
Why this work is in the frame
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Bibliographic record
Abstract
alpha1 Proteinase inhibitor (alpha1PI), a natural inhibitor of the serine proteinase leukocyte elastase, is also an intravenous therapeutic agent used to treat hereditary emphysema and may be useful in other respiratory disorders. However, to achieve sustained suppression of leukocyte elastase, alpha1PI must be given frequently and in large amounts, thus limiting its clinical use. We hypothesized that conjugating alpha1PI with polyethylene glycol (PEG) at Cys(232) could extend the in vivo half-life of alpha1PI in blood and lung. We present evidence that site-specific conjugation with either 20 or 40 kD PEG at Cys(232) of nonglycosylated recombinant human alpha1PI (rhalpha1PI) results in an active inhibitor with prolonged in vivo stability. In addition, 72 h after airway instillation PEG-rhalpha1PI was found to be significantly better than glycosylated alpha1PI in protecting the lung against leukocyte elastase-mediated lung hemorrhage. We conclude that thiol-specific PEGylation markedly improves the in vivo pharmacokinetic profile of rhalpha1PI and represents a simple, novel strategy to address the therapeutic goal of human leukocyte elastase inhibition.
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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 | 0.001 |
| 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 it