Relationship between peptide structure and antimicrobial activity as studied by de novo designed peptides

Abstract

As fundamental components in innate immunity, antimicrobial peptides (AMPs) hold great potentials in the treatment of persistent infections involving slow-growing or dormant bacteria in which, selective inhibition of prokaryotic bacteria in the context of eukaryotic cells is not only an essential requirement, but also a critical challenge in the development of antimicrobial peptides. To identify the sequence and structural properties critical for antimicrobial activity, a series of peptides varying in sequence, length, hydrophobicity/charge ratio, and secondary structure, were designed and synthesized. Their antimicrobial activities were then tested using Escherichia coli and HEK293 cells, together with several index activities against model membrane, including liposome leakage, fusion, and aggregation. While no evident correlation between the antimicrobial activity and the property of the peptides was observed, common activities against model membrane were nevertheless identified for the active antimicrobial peptides: mediating efficient membrane leakage, negligible membrane fusion and liposome aggregation. Therefore, in addition to identifying one highly active antimicrobial peptide, our study further sheds light on the design principle for these molecules.