Stability, toxicity, and biological activity of host defense peptide BMAP28 and its inversed and retro‐inversed isomers
Bibliographic record
Abstract
Host defense peptides (HDPs) contribute to immune defense through direct antimicrobial activity as well as modulation of host immune responses. While the antimicrobial activity of HDPs has been successfully exploited as topical antibiotics, their use as systemic immunomodulatory antimicrobials has been limited by their toxicity and biological instability. Peptide modification strategies to address these characteristics, while maintaining biological activity, are likely essential to capture the full therapeutic potential of HDPs. Here we investigate the stability, toxicity, and biological activity of the L, inversed (D), and retro-inversed (RI) isomers of BMAP28. The D and RI isomers both form symmetrically related structures to L BMAP28 and resist proteolytic degradation. With respect to toxicity, the considerable hemolytic activity of L BMAP28 is approximately halved with the D isomer and eliminated with RI BMAP28. Furthermore, while D BMAP28 maintains the same cytotoxicity profile against epithelial cells and monocytes as the natural peptide, RI BMAP28 is markedly less toxic against these cell types. As prophylactic antimicrobials, all three isomers significantly reduced bacterial loads [99.99% bacterial clearance by each peptide at the highest dose (20 mg kg(-1) )], when administered 18 h prior to challenge in a mouse model of peritoneal infection. This protection appears to be mediated through neutrophil recruitment and activation of macrophages for bacterial clearance. Collectively, the increased stability and retained biological activity of D and RI BMAP28 make these isomers attractive as antimicrobial therapeutics. In particular, the protection conferred by RI BMAP28, combined with its reduced toxicities, make it a strong candidate for further consideration.
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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) | 0.001 | 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".