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Multivalent display of the antimicrobial peptides BP100 and BP143

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-NH2 (BP100) and KKLfKKILKYL-NH2 (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

Beilstein Journal of Organic Chemistry, 2012, vol. 8, p. 2106-2117

Beilstein-Institut

Author: Güell Costa, Imma
Ferre Malagon, Rafael
Sørensen, Kasper K.
Badosa Romañó, Esther
Ng-Choi, Iteng
Montesinos Seguí, Emilio
Bardají Rodríguez, Eduard
Feliu Soley, Lídia
Jensen, Knud J.
Planas i Grabuleda, Marta
Date: 2012
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-NH2 (BP100) and KKLfKKILKYL-NH2 (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
Format: application/pdf
ISSN: 1860-5397 (versió paper)
1860-5397 (versió electrònica)
Document access: http://hdl.handle.net/10256/8561
Language: eng
Publisher: Beilstein-Institut
Collection: Reproducció digital del document publicat a: http://dx.doi.org/10.3762/bjoc.8.237
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Is part of: Beilstein Journal of Organic Chemistry, 2012, vol. 8, p. 2106-2117
Rights: Attribution 3.0 Spain
Rights URI: http://creativecommons.org/licenses/by/3.0/es/
Subject: Pèptids -- Síntesi
Antibiòtics pèptids
Peptides -- Synthesis
Peptide antibiotics
Title: Multivalent display of the antimicrobial peptides BP100 and BP143
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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