Screening and Characterization of Surface-Tethered Cationic Peptides for Antimicrobial Activity

Kai Hilpert, Melissa Elliott, Håvard Jenssen, Jason Kindrachuk, Christopher D. Fjell, Jana Körner, Dirk F.H. Winkler, Lindsay L. Weaver, Peter Henklein, Anne S. Ulrich, Sandy H.Y. Chiang, Susan W. Farmer, Nelly Pante, Rudolf Volkmer, Robert E.W. Hancock

Research output: Contribution to journalArticle

159 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)58-69
Number of pages12
JournalChemistry and Biology
Volume16
Issue number1
DOIs
Publication statusPublished - 30 Jan 2009

Keywords

  • CHEMBIO
  • MICROBIO

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this