Self-assembling organo-peptide bolaphiles with KLK tripeptide head groups display selective antibacterial activity

In keeping with recent efforts to generate compounds for antibiotic and microbicide development, we focused on the creation of non-natural organo-peptide hybrids of antimicrobial peptide amides (KLK(L)n KLK-NH2 ) derived from sapecin B and a self-assembling oligoglycine organo-peptide bolaphile containing an ω-amino fatty acid residue. The hybrid organo-peptide bolaphiles with two cationic KLK tripeptide motifs linked with an ω-amino acid residue (penta-, octa- or undecamethylene chain) maintained the self-assembling properties of the root oligoglycine bolaphile. Electron microscopy clearly revealed complex supramolecular architectures for both sapecin B-derived peptides and the hybrid analogues. FT-IR spectroscopy indicated that the supramolecular structures were composed primarily of β-sheets. CD revealed that the hybrid bolaphiles did not share the same secondary structures as the sapecin B peptides in solution. However, although secondary structures of antimicrobial peptides are central in the activity, the organo-peptide bolaphiles also retained the potent antimicrobial activity of the leader sapecin B-derived peptide against both Gram-positive and Gram-negative bacteria. In general, the hybrids were more selective than the sapecin B peptides, as they displayed little or no appreciable haemolytic activity. The results obtained herald a new approach for the design of purpose-built hybrid organo-peptide bolaphiles.