Use of Amphipathic Helical Peptides as An Anticoagulant
Bibliographic record
Abstract
Abstract We have previously shown that an ideal amphipathic helical peptide of K7L15 composition (IAP) accelerates factor IXa-mediated factor X turnover and factor Xamediated prothrombin turnover in a phospholipid free system (Biochem J., 2008, 412:545). Under these conditions, IAP behaves as a phospholipid membrane allowing coagulation factors to bind and exert their actions. However, when IAP is used with in vitro assays that employ phospholipids such as an active partial thromboplastin time (aPTT), IAP paradoxically behaves as an anticoagulant by prolonging clotting times. We hypothesize that this anticoagulant effect occurs by blocking binding sites for coagulation factors on phospholipids membranes. To test this hypothesis, we employed three phopholipid-dependant coagulation assays, the aPTT, dilute PT and dilute RVV, with both low and high concentrations of phospholipids. We show that these coagulation times are prolonged by IAP in a concentration dependent manner and that this prolongation is abrogated by adding excess phospholipid, demonstrating phospholpid dependence for this inhibition. In purified tenase and prothrombinase assays, in the presence of phospholipids, IAP inhibits substrate turnover consistent with our hypothesis. To show direct binding between IAP and phospholipids, we conducted fluorescence spectroscopy experiments and show direct binding between IAP and phospholipid membranes. In summary, the above data demonstrate that IAP acts as an anticoagulant by blocking the interaction of coagulation factors with phospholipids membranes.
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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 | 0.000 | 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 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".