Tuning the activity of a short arg-trp antimicrobial Peptide by lipidation of a C- or N-terminal lysine side-chain

H Bauke Albada; Pascal Prochnow; Sandra Bobersky; Sina Langklotz; Patrick Schriek; Julia E Bandow; Nils Metzler-Nolte

doi:10.1021/ml300148v

Tuning the activity of a short arg-trp antimicrobial Peptide by lipidation of a C- or N-terminal lysine side-chain

ACS Med Chem Lett. 2012 Sep 4;3(12):980-4. doi: 10.1021/ml300148v. eCollection 2012 Dec 13.

Authors

H Bauke Albada¹, Pascal Prochnow¹, Sandra Bobersky¹, Sina Langklotz¹, Patrick Schriek¹, Julia E Bandow¹, Nils Metzler-Nolte¹

Affiliation

¹ Inorganic Chemistry I-Bioinorganic Chemistry, Department of Chemistry and Biochemistry, and Group Microbial Antibiotic Research, Faculty for Biology and Biotechnology, Ruhr University Bochum , Universitätsstrasse 150, 44780 Bochum, Germany.

Abstract

The attachment of lipids to C- or N-terminally positioned lysine side-chain amino groups increases the activity of a short synthetic (Arg-Trp)3 antimicrobial peptide significantly, making these peptides even active against pathogenic Gram-negative bacteria. Thus, a peptide with strong activity against S. aureus (1.1-2 μM) and good activity against A. baumannii and P. aeruginosa (9-18 μM) was identified. The most promising peptide causes 50% hemolysis at 285 μM and shows some selectivity against human cancer cell lines. Interestingly, the increased activity of ferrocenoylated peptides is mostly due to the lipophilicity of the organometallic fragment.

Keywords: Lipidated antimicrobial peptides; anticancer; ferrocenoyl; nonhemolytic.