PCFT‐Independent Cellular Uptake of Cyclic Cell‐Penetrating Peptide‐Conjugated Folic Acid
Bibliographic record
Abstract
Folic acid is an essential component of many metabolic processes, including the synthesis of nucleoproteins, purines, and pyrimidines, and is a recommended supplement to lower the incidence of various disorders. Folic acid and folate-loaded nanoparticles are extensively evaluated for sustained release and enhanced stability of the molecule; however, malfunctioning of proton-coupled folate transporters (PCFTs) present on the intestinal cells and subsequent folate deficiency remain a major issue in this context. This study provides the first demonstration where cell-penetrating peptide-conjugated folic acid mediates PCFT-independent folic acid permeabilization and intracellular bioavailability in vitro in the intestinal cells and macrophages. Cyclic-transactivating transcriptional activator (cTAT) folic acid conjugates are prepared by solid-phase peptide synthesis and are evaluated for the cellular uptake and bioavailability in the presence and absence of PCFT inhibitors. Compared with free folic acid that showed PCFT-mediated cellular uptake, cTAT-folic acid conjugates exhibited enhanced cellular uptake at all studied pH and improved intracellular bioavailability of the cargo, as was determined by dihydrofolate reductase (DHFR) assay. Folic acid and cTAT-folic acid conjugates also dampened the production of proinflammatory mediators in the presence of toxins in vitro in macrophage cell lines.
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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 | 0.001 |
| 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".