Shortened cecropin A‐melittin hybrids Significant size reduction retains potent antibiotic activity

Abstract

We have earlier reported two 26‐residue antibacterial peptides made up from different segments ol'cecropin A (CA) and melittin (M). We now report a substantial reduction in size at the C‐terminal section of the highly active hybrid CA(1–8)M(1–18), leading to a series of 20‐, 18‐ and 15‐residue analogs with antibiotic properties similar to the larger molecule. In particular, the 15‐residue hybrids CA(1–7)M(2–9), CA(1–7)M(4–11) and CA(1–7)M(5–12) are the shortest cecropin‐based peptide antibiotics described so far, with antibacterial activity and spectra similar or better than cecropin A and a 60% reduction in size. Their reduced size and highly α‐helical structure require an alternative mechanism for their interaction with bacterial membranes.

Antibacterial activity of peptides homologous to a loop region in human lactoferrin

“…Some, like lactoferricin and HLTI, have their charged residues on one side of the helix and it is their helical nature rather than their chirality which is critical [27,28]. Monomeric HLT2 appears too short to span a bacterial membrane although other synthetic amphipathic ahelical peptides as short as 9 [29] and 15 [30] residues retain bactericidal activity. However, it is possible that these shorter peptides have a different mechanism of action [29,30].…”

Antibacterial activity of secretolytin, a chromogranin B‐derived peptide (614–626), is correlated with peptide structure

“…fluorescence spectroscopy, NMR), a non-pore mechanism was suggested as a possible mode of action of magainins [31], dermaseptin [24] and insect cecropins [14]. Further support for non-pore mechanism as the mode of action comes from the finding that cecropin-mellitin hybrids as short as 15 amino acids [32], or the 12 amino acid N-terminal analogue of dermaseptin [33] had antibacterial activity similar to that displayed by their intact parent molecules. The antibacterial characterization of secretolytin and PMAP-37 provides further examples arguing for the non-pore mechanism.…”

Interaction and Lipid-Induced Conformation of Two Cecropin−Melittin Hybrid Peptides Depend on Peptide and Membrane Composition

“…Taking CA(1-8)M(1-18) as lead, a subsequent approach was to further reduce the size of the hybrid CA-M peptides while retaining antimicrobial activity. This led to CA-(1-7)M(2-9), 9 a pentadecapeptide that preserves most of the activity of CA(1-8)M (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”