Simplified lipid II-binding antimicrobial peptides: Design, synthesis and antimicrobial activity of bioconjugates of nisin rings A and B with pore-forming peptides

Bioorg Med Chem. 2018 Nov 15;26(21):5691-5700. doi: 10.1016/j.bmc.2018.10.015. Epub 2018 Oct 19.

Abstract

New designs of antimicrobial peptides are urgently needed in order to combat the threat posed by the recent increase of resistance to antibiotics. In this paper, we present a new series of antimicrobial peptides, based on the key structural features of the lantibiotic nisin. We have simplified the structure of nisin by conjugating the lipid II-binding motif at the N-terminus of nisin to a series of cationic peptides and peptoids with known antibacterial action and pore-forming properties. Hybrid peptides, where a hydrophilic PEG4 linker was used, showed good antibacterial activity against Micrococcus luteus.

Keywords: Antimicrobial peptide; Bioconjugates; Cationic peptide; Lantibiotics; Peptoid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemical synthesis
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacillus subtilis / drug effects
  • Escherichia coli / drug effects
  • Micrococcus luteus / drug effects
  • Nisin / analogs & derivatives*
  • Nisin / chemical synthesis
  • Nisin / pharmacology*
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Peptoids / chemical synthesis
  • Peptoids / chemistry
  • Peptoids / pharmacology*
  • Pseudomonas aeruginosa / drug effects

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Peptide Fragments
  • Peptoids
  • Nisin