The major concern caused by pathogens bearing increasingly resistant to multi-antibiotics has motivated researchers to develop new antibiotics, including antimicrobial peptides (AMPs) 1. Due to their unique biological features, which included stimulating macrophages, the proline-rich AMPs (PrAMPs) family has been extensively studied as potential agents for the production of a new generation of antibiotics 2,3.
We undertook to better understand the mode of interaction of the de novo designed PrAMP, Chex1-Arg20, and its discontinuous dimer, A3-APO with Gram-negative E. coli membrane/model membrane interaction and their permeability. For comparison, a disulfide dimer of A3-APO was also examined [3]. We showed by high resolution microscopy and flow cytometry that there was an alteration of mechanism of antibacterial action on Gram-negative E. coli membrane/model membrane of a designed proline-rich antimicrobial peptide (PrAMP), Chex1-Arg20, with increasing valency from monomer to dimer and tetramer. Furthermore, Chex1-Arg20 and multimers displayed differences in E. coli membrane/model membrane potential. Such altered properties of these multimers advance on understanding of this type of AMP and suggest significant potential for the further development of novel PrAMPs.