Design and Synthesis of Lasso-Inspired Peptides with Antibacterial Activity
Bibliographic record
Abstract
Microcin J25 (MccJ25) is a 21-residue ribosomally synthesized bactericidal peptide produced by Escherichia coli strains with an unusual lariat protoknot structure [1]. MccJ25 exhibits bactericidal activity toward several Gram-negative food-borne pathogens, including Salmonella, Shigella and E. coli [2]. The particular lasso topology of MccJ25 makes the peptide highly resistant to denaturation by high temperatures or proteolysis. These are attractive properties to both pharmaceutical and food industries. MccJ25 structure consists of an 8-residue cycle (lariat ring) formed by a lactam bond between the N-terminal amine and the Glu side chain, which is followed by a 13-residue tail that loops back to thread through the ring (Figure 1). The C-terminal tail (residues 9-21) of the peptide is tightly trapped in the lariat ring due to the presence of two aromatic side chains at positions 19 and 20. RNA polymerase appears to be the principal intracellular target of MccJ25 but other mode of actions have also been identified including inhibition of the respiratory chain [3-5]. SAR studies by site-directed mutagenesis revealed that the inhibitory activity of MccJ25 tolerates a number of residue substitutions [6]. Recent attempts to produce the lasso structure of MccJ25 by chemical synthesis have not yielded successful microbial inhibitors. Nevertheless, two synthetic peptides derived from MccJ25 without lasso folding were found to be bactericidal [7]. The current lack of information on MccJ25 structure and its essential features for antimicrobial activity could be overcome by chemical engineering and computational studies. We hypothesized that lasso formation is important but not a prerequisite for the activity of MccJ25 and that it may be possible to obtain derivatives that are active without the lasso structure [8]. In this study, we report synthetic peptides based on the MccJ25 sequence but devoid of lasso folding yet retaining activity against bacteria (S. enterica and E. coli) and specific intracellular targets (RNA polymerase and the respiration chain).
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".