Design and Characterization of a Broad -Spectrum Bactericidal Acyl-lysyl Oligomer

Liran Livne, Tchelet Kovachi, Hadar Sarig, Raquel F. Epand, Fadia Zaknoon, Richard M. Epand, Amram Mor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Previously characterized chemical mimics of host defense peptides belonging to the oligo-acyl-lysyl (OAK) family have so far failed to demonstrate broad-spectrum antibacterial potency combined with selectivity toward host cells. Here, we investigated OAK sequences and characterized a promising representative, designated C12K-3β10, with broad-spectrum activity (MIC90 = 6.2 μM) and low hemotoxicity (LC50 > 100 μM). Whereas C12K-3β10 exerted an essentially bactericidal effect, E. coli bacteria were killed faster than S. aureus (minutes versus hours). Mechanistic studies addressing this difference revealed that unlike E. coli, S. aureus bacteria undergo a transient rapid bactericidal stage that over time converts to a bacteriostatic effect. This behavior was dictated by interactions with cell wall-specific components. Preliminary efficacy studies in mice using the thigh infection model demonstrated the OAK's ability to significantly affect bacterial viability upon single-dose systemic treatment (2 mg/kg).

Original languageEnglish
Pages (from-to)1250-1258
Number of pages9
JournalChemistry and Biology
Issue number12
StatePublished - 24 Dec 2009
Externally publishedYes




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