Cellular Activity of CQWW Nullomer-Derived Peptides
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide Analysis of observed protein sequences across all species within the UniProtKB/Swiss-Prot data set reveals CQWW as the shortest absent stretch of amino acids. While DNA can be found encoding the CQWW sequence, it has never been observed to be translated or included in manually curated sets of proteins, existing only in predicted, tentative sequences and in a single mature antibody sequence. We have synthesized this “nullomer” peptide, along with 13 derivatives, reversed, truncated, stereoisomers, and alanine-scanning peptides, conjugated to polyarginine stretches to increase cellular uptake. We observed their impact against a healthy neuronal line and six patient-derived glioblastoma cell lines spanning three clinical subtypes. Results reveal IC 50 values averaging 4.9 μM for inhibition of cell survival across tested oncogenic cell lines. High-content phenotypic analysis of cellular features and reverse-phase protein arrays failed to discern a clear mode of action for the nullomer peptide but suggests mitochondrial impairment through the inhibition of GSK3 and isoforms, supported by observations of reduced mitochondrial stain intensities. With a recent increase in interest in nullomer peptides, we see the results in this study as a starting point for further investigation into this potentially therapeutic peptide class.
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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 | 0.001 | 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 | 0.001 | 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".