Short cationic lipopeptides as effective antibacterial agents

Design, physicochemical properties and biological evaluation

Fazren Azmi, Alysha G. Elliott, Nirmal Marasini, Soumya Ramu, Zyta Ziora, Angela M. Kavanagh, Mark A T Blaskovich, Matthew A. Cooper, Mariusz Skwarczynski, Istvan Toth

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2235-2241
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume24
Issue number10
DOIs
Publication statusPublished - 15 May 2016

Fingerprint

Lipopeptides
Anti-Bacterial Agents
Bacteria
Gram-Positive Bacteria
Daptomycin
Peptides
Methicillin Resistance
Methicillin
Poisons
Vancomycin
Transmission Electron Microscopy
Pharmaceutical Preparations
Liver
Nanoparticles
Lysine
Extrusion
Cells
Transmission electron microscopy
Membranes
Kidney

Keywords

  • Amphiphilic
  • Antibacterial
  • Lipopeptide
  • Nanoparticle
  • Peptidomimetics

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

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; Toth, Istvan.

In: Bioorganic and Medicinal Chemistry, Vol. 24, No. 10, 15.05.2016, p. 2235-2241.

Research output: Contribution to journalArticle

Azmi, F, Elliott, AG, Marasini, N, Ramu, S, Ziora, Z, Kavanagh, AM, Blaskovich, MAT, Cooper, MA, Skwarczynski, M & Toth, I 2016, 'Short cationic lipopeptides as effective antibacterial agents: Design, physicochemical properties and biological evaluation', Bioorganic and Medicinal Chemistry, vol. 24, no. 10, pp. 2235-2241. https://doi.org/10.1016/j.bmc.2016.03.053
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. / Short cationic lipopeptides as effective antibacterial agents : Design, physicochemical properties and biological evaluation. In: Bioorganic and Medicinal Chemistry. 2016 ; Vol. 24, No. 10. pp. 2235-2241.
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