1 research outputs found
Lipo-γ-AApeptides as a New Class of Potent and Broad-Spectrum Antimicrobial Agents
There is increasing demand to develop antimicrobial peptides
(AMPs)
as next generation antibiotic agents, as they have the potential to
circumvent emerging drug resistance against conventional antibiotic
treatments. Non-natural antimicrobial peptidomimetics are an ideal
example of this, as they have significant potency and in vivo stability.
Here we report for the first time the design of lipidated γ-AApeptides
as antimicrobial agents. These lipo-γ-AApeptides show potent
broad-spectrum activities against fungi and a series of Gram-positive
and Gram-negative bacteria, including clinically relevant pathogens
that are resistant to most antibiotics. We have analyzed their structure–function
relationship and antimicrobial mechanisms using membrane depolarization
and fluorescent microscopy assays. Introduction of unsaturated lipid
chain significantly decreases hemolytic activity and thereby increases
the selectivity. Furthermore, a representative lipo-γ-AApeptide
did not induce drug resistance in <i>S. aureus</i>, even
after 17 rounds of passaging. These results suggest that the lipo-γ-AApeptides
have bactericidal mechanisms analogous to those of AMPs and have strong
potential as a new class of novel antibiotic therapeutics