Screening and characterization of surface-tethered cationic peptides for antimicrobial activity.
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.
Hilpert
Kai
K
Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
Elliott
Melissa
M
Jenssen
Håvard
H
Kindrachuk
Jason
J
Fjell
Christopher D
CD
Körner
Jana
J
Winkler
Dirk F H
DF
Weaver
Lindsay L
LL
Henklein
Peter
P
Ulrich
Anne S
AS
Chiang
Sandy H Y
SH
Farmer
Susan W
SW
Pante
Nelly
N
Volkmer
Rudolf
R
Hancock
Robert E W
RE
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
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002482:Cellulose; C008079:hydroxypropylcellulose