Structure-Activity Relationships of Antibacterial Acyl-Lysine Oligomers

Inna S. Radzishevsky, Tchelet Kovachi, Yaara Porat, Lior Ziserman, Fadia Zaknoon, Dganit Danino, Amram Mor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


We describe structure-activity relationships that emerged from biophysical data obtained with a library of antimicrobial peptide mimetics composed of 103 oligoacyllysines (OAKs) designed to pin down the importance of hydrophobicity (H) and charge (Q). Based on results obtained with OAKs displaying minimal inhibitory concentration ≤ 3 μM, the data indicate that potent inhibitory activity of the gram-negative Escherichia coli and the gram-positive Staphylococcus aureus required a relatively narrow yet distinct window of HQ values where the acyl length played multiple and critical roles, both in molecular organization and in selective activity. Thus, incorporation of long-but not short-acyl chains within a peptide backbone is shown to lead to rigid supramolecular organization responsible for poor antibacterial activity and enhanced hemolytic activity. However, sequence manipulations, including introduction of a tandem lysine motif into the oligomer backbone, enabled disassembly of aggregated OAKs and subsequently revealed tiny, nonhemolytic, yet potent antibacterial derivatives.

Original languageEnglish
Pages (from-to)354-362
Number of pages9
JournalChemistry and Biology
Issue number4
StatePublished - 21 Apr 2008
Externally publishedYes




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