Improving the biological activity of the antimicrobial peptide anoplin by membrane anchoring through a lipophilic amino acid derivative.

Abstract

The lipophilic amino acid, (S)-2-aminoundecanoic acid, was synthesized and incorporated at a number of specific positions within the peptide sequence of anoplin. These lipophilic anoplin analogs showed to be more active against Escherichia coli and Staphylococcus aureus compared to native anoplin, while the EC50-value of hemolysis was at least one order of magnitude lower than the MIC values. This was in sharp contrast to the N-acylated anoplin derivative, where a gain in activity also led to a complete loss of selectivity. Thus, the incorporation of a lipophilic amino acid residue into anoplin enhanced the antimicrobial activity, while selectivity towards microbial membranes was retained.

• Authors: Jack C Slootweg, Timo B van Schaik, H Linda C Quarles van Ufford, Eefjan Breukink, Rob M J Liskamp, Dirk T S Rijkers
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 13 Pg. 3749-52 (Jul 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 23719232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Antimicrobial Cationic Peptides
• Wasp Venoms
• anoplin

Topics

• Anti-Bacterial Agents (chemical synthesis, chemistry, pharmacology)
• Antimicrobial Cationic Peptides (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Escherichia coli (drug effects)
• Hydrophobic and Hydrophilic Interactions
• Microbial Sensitivity Tests
• Molecular Conformation
• Staphylococcus aureus (drug effects)
• Structure-Activity Relationship
• Wasp Venoms (chemical synthesis, chemistry, pharmacology)