Structure-Activity Relationship Study to Develop Peptide Amphiphiles as Species-Specific Antimicrobials

Aramis J. Pereira, Huihua Xing, Luana J. de Campos, Mohamed A. Seleem, Kelly M.P. de Oliveira, Stephen K. Obaro, Martin Conda-Sheridan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Antimicrobial peptide amphiphiles (PAs) are a promising class of molecules that can disrupt the bacterial membrane or act as drug nanocarriers. In this study, we prepared 33 PAs to establish supramolecular structure-activity relationships. We studied the morphology and activity of the nanostructures against different Gram-positive and Gram-negative bacterial strains (such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii). Next, we used principal component analysis (PCA) to determine the key contributors to activity. We found that for S. aureus, the zeta potential was the major contributor to the activity while Gram-negative bacteria were more influenced by the partition coefficient (LogP) with the following order P. aeruginosa>E. coli>A. baumannii. We also performed a study of the mechanism of action of selected PAs on the bacterial membrane assessing the membrane permeability and depolarization, changes in zeta potential and overall integrity. We studied the toxicity of the nanostructures against mammalian cells. Finally, we performed an in vivo study using the wax moth larvae to determine the therapeutic efficacy of the active PAs. This study shows cationic PA nanostructures can be an intriguing platform for the development of nanoantibacterials.

Original languageEnglish (US)
Article numbere202303986
JournalChemistry - A European Journal
Issue number15
StatePublished - Mar 12 2024


  • antimicrobial peptide amphiphile
  • species-specific
  • supramolecular nanostructures

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Organic Chemistry


Dive into the research topics of 'Structure-Activity Relationship Study to Develop Peptide Amphiphiles as Species-Specific Antimicrobials'. Together they form a unique fingerprint.

Cite this