Novel imidazolium salt--peptide conjugates and their antimicrobial activity

Bioconjug Chem. 2014 Dec 17;25(12):2166-74. doi: 10.1021/bc500510c. Epub 2014 Dec 8.

Abstract

Our study presents innovative research dealing with the synthesis and biological evaluation of conjugates out of antimicrobial peptides (AMPs) and imidazolium cations that are derived from ionic liquids. AMPs are considered as promising alternatives to common antibiotics due to their different activity mechanisms. Antibacterial effects have also been described for ionic liquids bearing imidazolium cations . Besides single coupling of carboxy-functionalized imidazolium cations to the peptide N-terminal we also developed conjugates bearing multiple copies of imidazolium cations. The combination of both compounds resulted in synergistic effects that were most pronounced when more imidazolium cations were attached to the peptides. In addition, antibacterial activity even in drug-resistant bacterial strains could be observed. Moreover, the novel compounds showed good selectivity only against bacterial cells, an observation that was further proven by lipid interaction studies using giant unilamellar vesicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / pharmacology*
  • Drug Resistance, Bacterial / drug effects
  • Erythrocytes
  • Humans
  • Imidazoles / chemistry*
  • Ionic Liquids / chemistry
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / pharmacology
  • Salts / chemistry
  • Solid-Phase Synthesis Techniques
  • Structure-Activity Relationship

Substances

  • Anti-Infective Agents
  • Imidazoles
  • Ionic Liquids
  • Peptides
  • Salts