Tuning the Activity of Anoplin by Dendrimerization of Lysine and Lipidation of the N-Terminal

Abstract

Dendrimeric antimicrobial peptides or lipopeptides have strong transmembrane ability and antibacterial activity. To obtain some ideal antimicrobial peptides, anoplin, a natural antimicrobial peptide with weak antimicrobial activity, was modified by C-terminal dendrimerization using lysine and N-terminal lipidation using fatty acids. 2K-3A-C4, a trimer of anoplin, was dendrimerized by two lysines at the C-terminal and was lipidated by n -butyric acid at the N-terminal, and thus exhibited the best antibacterial activity. However, the trimer had high hemolytic activity. Finally, A-C8, a simple structural lipopeptide, which is not a dendrimer, was obtained following the lipidation of anoplin using octanoic acid; it exhibited the highest therapeutic index, which makes it a probable antibiotic and thus was screened out.

The Potential of Modified and Multimeric Antimicrobial Peptide Materials as Superbug Killers

“…Branched AMPs can be formed through several methods and show improved activity. Comparison of dimeric (K-2A), trimeric (2K-3A), and tetrameric (3K-4A) anoplin, which were additionally lipidated at the N-terminal, revealed the trimer with n -butyric acid (2K-3A-C4) to have the best antibacterial activity ( Gou et al, 2021 ). All of the multimers were built from a branched lysine core and tested against S. aureus , B. subtilis , E. coli , P. aeruginosa and K. pneumoniae.…”