Combining topology and sequence design for the discovery of potent antimicrobial peptide dendrimers against multidrug-resistant Pseudomonas aeruginosa

Angew Chem Int Ed Engl. 2014 Nov 17;53(47):12827-31. doi: 10.1002/anie.201409270. Epub 2014 Oct 24.

Abstract

Multidrug-resistant opportunistic bacteria, such as Pseudomonas aeruginosa, represent a major public health threat. Antimicrobial peptides (AMPs) and related peptidomimetic systems offer an attractive opportunity to control these pathogens. AMP dendrimers (AMPDs) with high activity against multidrug-resistant clinical isolates of P. aeruginosa and Acinetobacter baumannii were now identified by a systematic survey of the peptide sequences within the branches of a distinct type of third-generation peptide dendrimers. Combined topology and peptide sequence design as illustrated here represents a new and general strategy to discover new antimicrobial agents to fight multidrug-resistant bacterial pathogens.

Keywords: Pseudomonas aeruginosa; antibiotics; antimicrobial peptides; dendrimers; peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / chemical synthesis
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Dendrimers / chemical synthesis
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Drug Discovery*
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Pseudomonas aeruginosa / drug effects*
  • Structure-Activity Relationship

Substances

  • Antimicrobial Cationic Peptides
  • Dendrimers