title: Multivalent display of the antimicrobial peptides BP100 and BP143.
abstract: Carbohydrates are considered as promising templates for the display of multiple copies of antimicrobial peptides. Herein, we describe the design and synthesis of chimeric structures containing two or four copies of the antimicrobial peptides KKLFKKILKYL-NH(2) (BP100) and KKLfKKILKYL-NH(2) (BP143) attached to the carbohydrate template cyclodithioerythritol (cDTE) or α-D-galactopyranoside (Galp). The synthesis involved the preparation of the corresponding peptide aldehyde followed by coupling to an aminooxy-functionalized carbohydrate template. After purification, the multivalent display systems were obtained in high purities (90-98%) and in good yields (42-64%). These compounds were tested against plant and human pathogenic bacteria and screened for their cytotoxicity on eukaryotic cells. They showed lower MIC values than the parent peptides against the bacteria analyzed. In particular, the carbopeptides derived from cDTE and Galp, which contained two or four copies of BP100, respectively, were 2- to 8-fold more active than the monomeric peptide against the phytopathogenic bacteria. These results suggest that preassembling antimicrobial peptides to multimeric structures is not always associated with a significant improvement of the activity. In contrast, the carbopeptides synthesized were active against human red blood cells pointing out that peptide preassembly is critical for the hemolytic activity. Notably, peptide preassembly resulted in an enhanced bactericidal effect.
authors.affiliation: LIPPSO, Department of Chemistry, University of Girona, Campus Montilivi, 17071 Girona, Spain.
authors.forename: Imma
authors.initials: I
authors.lastname: Güell
authors.forename: Rafael
authors.initials: R
authors.lastname: Ferre
authors.forename: Kasper Kildegaard
authors.initials: KK
authors.lastname: Sørensen
authors.forename: Esther
authors.initials: E
authors.lastname: Badosa
authors.forename: Iteng
authors.initials: I
authors.lastname: Ng-Choi
authors.forename: Emilio
authors.initials: E
authors.lastname: Montesinos
authors.forename: Eduard
authors.initials: E
authors.lastname: Bardají
authors.forename: Lidia
authors.initials: L
authors.lastname: Feliu
authors.forename: Knud J
authors.initials: KJ
authors.lastname: Jensen
authors.forename: Marta
authors.initials: M
authors.lastname: Planas