Antimicrobial peptides (AMPs) are the defensive weapons of the innate immune system wielded against pathogenic microbes in virtually every organism. The biological activity of AMPs has been well explored with many AMPs exhibiting cytolytic activity towards mammalian cells, which has limited their use as therapeutic agents to date. Several models have been proposed for the mode of antimicrobial action, however, little direct structural evidence is available in membrane-mimetic models systems. Several classes of AMPs self-assemble into helical filaments. In at least one case, the cytolytic activity of the AMP toward mammalian cell lines is significantly reduced while the antimicrobial activity is retained. However, due to the lack of structural information, little direct insight has been available to either guide the design of therapeutic AMP assemblies or to understand the basis of their antimicrobial activity. Here we present the structural analysis of filamentous peptide assemblies and their design principles that we believe to be necessary for the biological activity of this class of peptides. Continued structural analysis of these filaments may illuminate the mechanism through which the peptides exert their influence in a membrane environment. In practice, the corresponding filaments could serve as a matrix for controlled release of AMPs that minimizes the cytolytic response toward mammalian cells.

Investigating the relationship between peptide assemblies and antimicrobial activity

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.