Antimicrobial peptides (AMPs), known as host defence peptides, are potentially potent alternatives to conventional antibiotics, given their broad spectrum of activity. They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures, resulting in permeability and destruction of target microorganism membranes. To further improve the antibacterial activity, we have applied different chemical modifications on several AMPs, including multimerisation, conjugation and lipidation. For example, the attachment of moderate-length lipid carbon chains to cationic peptides can assist peptide insertion into the membrane lipid bilayer, inducing curvature and resulting in membrane pore formation, destabilisation, depolarisation, and leakage. Our findings highlight the advantages of modern chemical biology methods in developing novel AMPs with more potent antibacterial activity.
In addition, the plant defensins are widely dispersed across the plant kingdom and are significant components of the plant’s innate immune system. Interestingly, unlike those found in insects and mammals, plant defensins commonly target fungi rather than bacteria. We are currently modifying a series of chimaera plant defensins to investigate their structure and antimicrobial activity against both bacteria and fungi. The knowledge generated will direct the novel antifungal/antibacterial design and combination therapies against infections.