Differential Binding of L- vs. D-isomers of Cationic Antimicrobial Peptides to the Biofilm Exopolysaccharide Alginate
Why this work is in the frame
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Bibliographic record
Abstract
Alginate is a biofilm exopolysaccharide secreted by the opportunistic pathogen Pseudomonas aeruginosa that acts to prevent the diffusion of antibiotics toward the bacterial cell membrane. Cationic antimicrobial peptides (CAPs) have been increasingly recognized as a viable alternative for prospective antimicrobial agents. The D-isomer chiral counterparts of active L-isomer CAPs tend to show slightly greater antimicrobial activities because bacteria lack proteases to hydrolyze the unnatural D-isomers. Using an enantiomeric pair of synthetic CAPs designed in our laboratory (L-4Leu in the sequence KKKKKKALFALWLAFLA-NH2 and its D-analog D-4Leu), we studied the binding and interactions of Lvs. D-isomers of CAPs with alginate using circular dichroism and Raman spectroscopic techniques. We found that the peptide D-4Leu underwent a more rapid structural transition over time from an initial alginate-induced α-helical conformation to a less soluble β-sheet conformation than L-4Leu, indicating that the D-isomer of this peptide has a relatively greater affinity for alginate. Through Raman spectroscopy it was observed that Raman modes at 1297 cm-1 and 1453 cm-1 wavenumbers were found to differ between the spectra obtained from the insoluble complexes formed between L-4Leu vs. D-4Leu and alginate. These modes were tentatively assigned to CH, and CH3 deformation modes, respectively. Our findings reveal previously undetected subtleties in the binding of this diastereomeric pair of peptides in the microenvironment of a biofilm exopolysaccharide, and provide guidelines for future development of antimicrobial peptides.
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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