Short cationic lipopeptides as effective antibacterial agents: design, physicochemical properties and biological evaluation

Azmi, Fazren, Elliott, Alysha G., Marasini, Nirmal, Ramu, Soumya, Ziora, Zyta, Kavanagh, Angela M., Blaskovich, Mark A. T., Cooper, Matthew A., Skwarczynski, Mariusz and Toth, Istvan (2016) Short cationic lipopeptides as effective antibacterial agents: design, physicochemical properties and biological evaluation. Bioorganic and Medicinal Chemistry, 24 10: 2235-2241. doi:10.1016/j.bmc.2016.03.053


Author Azmi, Fazren
Elliott, Alysha G.
Marasini, Nirmal
Ramu, Soumya
Ziora, Zyta
Kavanagh, Angela M.
Blaskovich, Mark A. T.
Cooper, Matthew A.
Skwarczynski, Mariusz
Toth, Istvan
Title Short cationic lipopeptides as effective antibacterial agents: design, physicochemical properties and biological evaluation
Journal name Bioorganic and Medicinal Chemistry   Check publisher's open access policy
ISSN 1464-3391
0968-0896
Publication date 2016-05-11
Sub-type Article (original research)
DOI 10.1016/j.bmc.2016.03.053
Open Access Status Not Open Access
Volume 24
Issue 10
Start page 2235
End page 2241
Total pages 7
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon Press
Collection year 2017
Language eng
Formatted abstract
The spread of drug-resistant bacteria has imparted a sense of urgency in the search for new antibiotics. In an effort to develop a new generation of antibacterial agents, we have designed de novo charged lipopeptides inspired by natural antimicrobial peptides. These short lipopeptides are composed of cationic lysine and hydrophobic lipoamino acids that replicate the amphiphilic properties of natural antimicrobial peptides. The resultant lipopeptides were found to self-assemble into nanoparticles. Some were effective against a variety of Gram-positive bacteria, including strains resistant to methicillin, daptomycin and/or vancomycin. The lipopeptides were not toxic to human kidney and liver cell lines and were highly resistant to tryptic degradation. Transmission electron microscopy analysis of bacteria cells treated with lipopeptide showed membrane-damage and lysis with extrusion of cytosolic contents. With such properties in mind, these lipopeptides have the potential to be developed as new antibacterial agents against drug-resistant Gram-positive bacteria.
Keyword Amphiphilic
Antibacterial
Lipopeptide
Nanoparticle
Peptidomimetics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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