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Chemistry. 2016 Jun 6;22(24):8358-67. doi: 10.1002/chem.201600445. Epub 2016 May 4.

Incorporation of β-Silicon-β3-Amino Acids in the Antimicrobial Peptide Alamethicin Provides a 20-Fold Increase in Membrane Permeabilization.

Author information

1
Department of Chemistry and, Interdisciplinary Nanoscience Center, Center for Insoluble Protein Structures, Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.
2
Department of Molecular Biology and Genetics and, Interdisciplinary Nanoscience Center, Center for Insoluble Protein Structures, Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.
3
Department of Molecular Biology and Genetics and, Interdisciplinary Nanoscience Center, Center for Insoluble Protein Structures, Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark. dao@inano.au.dk.
4
Department of Chemistry and, Interdisciplinary Nanoscience Center, Center for Insoluble Protein Structures, Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark. ts@chem.au.dk.

Abstract

Incorporation of silicon-containing amino acids in peptides is known to endow the peptide with desirable properties such as improved proteolytic stability and increased lipophilicity. In the presented study, we demonstrate that incorporation of β-silicon-β3-amino acids into the antimicrobial peptide alamethicin provides the peptide with improved membrane permeabilizing properties. A robust synthetic procedure for the construction of β-silicon-β3-amino acids was developed and the amino acid analogues were incorporated into alamethicin at different positions of the hydrophobic face of the amphipathic helix by using SPPS. The incorporation was shown to provide up to 20-fold increase in calcein release as compared with wild-type alamethicin.

KEYWORDS:

amino acids; antibiotics; membrane proteins; peptidomimetics; silicon

PMID:
27144376
DOI:
10.1002/chem.201600445
[Indexed for MEDLINE]

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