A strategy of sequential dimerization of monomers of antimicrobial peptides (AMPs) into one polypeptide chain has been implemented on the example of a beta-structural AMP polyphemusin I which is one of the most effective candidate for use as an antibiotic. The possible polyphemusin I monomer and dimer structures in lipid membrane were studied in this work via molecular modeling. To this end, these molecules were chemically synthesized so that the dimer represented two monomers connected in series into one polypeptide chain with a flexible linker. The antimicrobial effects of monomer and dimer were then tested on various bacterial cultures, and their similarity was shown. Therefore, we can conclude that the pore formation is not a putative mechanism of the polyphemusin I action.
antimicrobial peptides, peptide dimerization, mechanism of antimicrobial action, polyphemusin
The work was supported by the Ministry of Science and Higher Education of the Russian Federation (Project Unique Identifier RFMEFI57517X0151).
Proof of pore formation and biophysical perturbations through a 2D amoxicillin-lipid membrane interaction approach
