title: 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.affiliation: Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Jack C
authors.initials: JC
authors.lastname: Slootweg
authors.forename: Timo B
authors.initials: TB
authors.lastname: van Schaik
authors.forename: H Linda C
authors.initials: HL
authors.lastname: Quarles van Ufford
authors.forename: Eefjan
authors.initials: E
authors.lastname: Breukink
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
authors.forename: Dirk T S
authors.initials: DT
authors.lastname: Rijkers
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014862:Wasp Venoms / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D014862:Wasp Venoms; C443041:anoplin