Engineered Assembliesfrom Constitutionally IsomericPeptides Modulate Antimicrobial Activity

Antimicrobial peptides (AMPs) are a class of peptides consisting of cationic amino acid residues and a hydrophobic segment, which have been used as an alternative to antibiotics in treating multidrug-resistant bacteria. However, the relationship among the molecular design, assembled structures, and resultant efficacy remains elusive. Herein, we report a class of constitutionally isomeric AMPs assembled into filaments with similar dimensions. Spectroscopic characterizations demonstrated that subtle changes in the position of amino acids led to dramatic variations in molecular packing and surface charges, which were verified by molecular dynamics simulations. In vitro antibacterial assays showed that all AMPs exerted antibacterial activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), but the efficacy was dependent on the molecular design. Given the good biocompatibility to eukaryotic cells, these AMPs could be potentially used as antibacterial agents. We believe that this finding provides an avenue to tune the bioactivity of AMPs by rational molecular design.