Antimicrobial Leucocin Analogues with a Disulfide Bridge Replaced by a Carbocycle or by Noncovalent Interactions of Allyl Glycine Residues
Bibliographic record
Abstract
The type IIa bacteriocins are antimicrobial peptides isolated from lactic acid bacteria that act as food preservation agents and have nanomolar activity against pathogens such as Listeria monocytogenes. Previous reports with mutant bacteriocins indicate that the conserved disulfide bridge between cysteine residues 9 and 14 in bacteriocins such as leucocin A (1) is critical for antibiotic properties, which are mediated by target membrane receptor proteins belonging to the mannose phosphotransferase (mpt) system. To examine whether the disulfide can be replaced by an olefin moiety, [9,14]-dicarba leucocin A (4) was made by on-resin ring closing metathesis of allyl glycine residues using a new protocol suitable for larger hydrophobic peptides. Carbocyclic analogue 4 still displays nanomolar activity but is about 10-fold less potent than 1. Surprisingly, the acyclic [9,14]-diallyl leucocin A (5) displays even higher antibiotic activity than 4 and is as effective as the parent, leucocin A (1). We attribute this activity to hydrophobic intermolecular interactions of the diallyl side chains of the acyclic bacteriocin 5 that assist realization of the correct conformation at the receptor active site. Such substitutions in other systems may allow linear acyclic peptides to mimic the biological activity of natural disulfide ring-containing parents.
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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".