title: Screening and characterization of surface-tethered cationic peptides for antimicrobial activity.
abstract: There is an urgent need to coat the surfaces of medical devices, including implants, with antimicrobial agents to reduce the risk of infection. A peptide array technology was modified to permit the screening of short peptides for antimicrobial activity while tethered to a surface. Cellulose-amino-hydroxypropyl ether (CAPE) linker chemistry was used to synthesize, on a cellulose support, peptides that remained covalently bound during biological assays. Among 122 tested sequences, the best surface-tethered 9-, 12-, and 13-mer peptides were found to be highly antimicrobial against bacteria and fungi, as confirmed using alternative surface materials and coupling strategies as well as coupling through the C and N termini of the peptides. Structure-activity modeling of the structural features determining the activity of tethered peptides indicated that the extent and positioning of positive charges and hydrophobic residues were influential in determining activity.
authors.affiliation: Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kai
authors.initials: K
authors.lastname: Hilpert
authors.forename: Melissa
authors.initials: M
authors.lastname: Elliott
authors.forename: Håvard
authors.initials: H
authors.lastname: Jenssen
authors.forename: Jason
authors.initials: J
authors.lastname: Kindrachuk
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Fjell
authors.forename: Jana
authors.initials: J
authors.lastname: Körner
authors.forename: Dirk F H
authors.initials: DF
authors.lastname: Winkler
authors.forename: Lindsay L
authors.initials: LL
authors.lastname: Weaver
authors.forename: Peter
authors.initials: P
authors.lastname: Henklein
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.forename: Sandy H Y
authors.initials: SH
authors.lastname: Chiang
authors.forename: Susan W
authors.initials: SW
authors.lastname: Farmer
authors.forename: Nelly
authors.initials: N
authors.lastname: Pante
authors.forename: Rudolf
authors.initials: R
authors.lastname: Volkmer
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002482:Cellulose / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D040081:Protein Array Analysis; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002482:Cellulose; C008079:hydroxypropylcellulose