Self-assembled cationic amphiphiles as antimicrobial peptides mimics: Role of hydrophobicity, linkage type, and assembly state

Yingyue Zhang, Ammar Algburi, Ning Wang, Vladyslav Kholodovych, Drym O. Oh, Michael Chikindas, Kathryn E. Uhrich

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Inspired by high promise using naturally occurring antimicrobial peptides (AMPs) to treat infections caused by antimicrobial-resistant bacteria, cationic amphiphiles (CAms) were strategically designed as synthetic mimics to overcome associated limitations, including high manufacture cost and low metabolic stability. CAms with facially amphiphilic conformation were expected to demonstrate membrane-lytic properties and thus reduce tendency of resistance development. By systematically tuning the hydrophobicity, CAms with optimized compositions exhibited potent broad-spectrum antimicrobial activity (with minimum inhibitory concentrations in low μg/mL range) as well as negligible hemolytic activity. Electron microscope images revealed the morphological and ultrastructure changes of bacterial membranes induced by CAm treatment and validated their membrane-disrupting mechanism. Additionally, an all-atom molecular dynamics simulation was employed to understand the CAm-membrane interaction on molecular level. This study shows that these CAms can serve as viable scaffolds for designing next generation of AMP mimics as antimicrobial alternatives to combat drug-resistant pathogens.

Original languageEnglish (US)
Pages (from-to)343-352
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Issue number2
StatePublished - Feb 1 2017

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science


  • Antimicrobial activity
  • Antimicrobial peptides
  • Membrane disruption
  • Self-assembly
  • Synthetic mimics


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