title: Combining topology and sequence design for the discovery of potent antimicrobial peptide dendrimers against multidrug-resistant Pseudomonas aeruginosa.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern (Switzerland).
authors.forename: Michaela
authors.initials: M
authors.lastname: Stach
authors.forename: Thissa N
authors.initials: TN
authors.lastname: Siriwardena
authors.forename: Thilo
authors.initials: T
authors.lastname: Köhler
authors.forename: Christian
authors.initials: C
authors.lastname: van Delden
authors.forename: Tamis
authors.initials: T
authors.lastname: Darbre
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Reymond
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D023181:Antimicrobial Cationic Peptides; D050091:Dendrimers
keywords: Pseudomonas aeruginosa; antibiotics; antimicrobial peptides; dendrimers; peptides