Publication Date
Fall 11-2025
Description
Cecropins are a class of antimicrobial peptides (AMPs) expressed by insects that have broad-spectrum antimicrobial activity and low cytotoxicity. However, cecropins are also long (40–45 amino acids) peptides, making their adaptation for therapeutic use challenging. Here, we present a series of 16 amino acid-long peptides derived from cecropin B from Drosophila melanogaster. The native truncated peptide is cationic and expected to form an amphipathic α-helix, but does not have antimicrobial activity. The incorporation of two Trp residues, depending on the position in the peptide backbone, results in antibacterial activity compa-rable to that of full-length cecropin B against the gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, Acinetobacterbaumannii, and Klebsiella pneumoniae, and there is minimal improvement as additional Trp substitutions are made. The incor-poration of three or four Trp residues results in antibacterial activity against Gram-positive bacteria Staphylococcus aureus andEnterococcus faecalis, which are not affected by the full-length peptide at tested concentrations. However, peptides containingthree or four Trp residues also had increased levels of cytotoxicity and hemolysis. NMR studies revealed an intrinsically disordered peptide in water, with some residual secondary structure. Secondary structure analysis by circular dichroism spectroscopy found that the propensity for helicity increases with increasing numbers of Trp residues, although individual Trp interactions at the C-terminal side of the peptide seem to have the biggest role in peptide structure. Similar to the full-length cecropin peptides, the truncated AMPs cause membrane permeability, but differences in the rate of permeabilization and bacterial killing do not directly correlate with the minimum inhibitory concentration (MIC) for each peptide. We propose that the location of the Trp residues, as opposed to the number incorporated, determines the antibacterial activity, and that peptide activity depends on the membrane composition of the bacteria.
Journal
Peptide Science
Volume
118
Issue
e70015
Department
Chemistry
Second Department
Biology
Link to Published Version
https://onlinelibrary.wiley.com/doi/epdf/10.1002/pep2.70015
DOI
10.1002/pep2.70015
Recommended Citation
Smith, Sarah; Feudale, Christopher; Vermillion, Josephina R.; Feudale, Joseph; Do, Joshua; Arroyo, Sabrina; Barrera, Juan; Whitsitt, Madeleine; Duval, Marion; Grames, Colby; Hatzinger, Bret; Hilling, MaKenzie; Kean, Tia; Rivera, JaSayle; Shum, Mia; Zyra, Hannah; Rovnyak, David; and Chambers, Moria C.. "Enhancement of Antimicrobial Activity of Truncated Cecropin B Peptides With the Substitution of Tryptophan Residues." (2025) .