Computational Design of Pore-Forming Peptides with Potent Antimicrobial and Anticancer Activities.

ABSTRACT: Peptides that form transmembrane barrel-stave pores are potential alternative therapeutics for bacterial infections and cancer. However, their optimization for clinical translation is hampered by a lack of sequence-function understanding. Recently, we have de novo designed the first synthetic barrel-stave pore-forming antimicrobial peptide with an identified function of all residues. Here, we systematically mutate the peptide to improve pore-forming ability in anticipation of enhanced activity. Using computer simulations, supported by liposome leakage and atomic force microscopy experiments, we find that pore-forming ability, while critical, is not the limiting factor for improving activity in the submicromolar range. Affinity for bacterial and cancer cell membranes needs to be opti

SUBMITTER: Deb R 

PROVIDER: S-EPMC11345766 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature