Analogous oligo-acyl-lysines with distinct antibacterial mechanisms

Shahar Rotem, Inna S. Radzishevsky, Dmitry Bourdetsky, Shiri Navon-Venezia, Yehuda Carmeli, Amram Mor

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Bactericidal properties were recently shown to emerge from hydrophobicity and charge buildup in oligo-acyl-lysine (OAK) peptide mimetics. Toward understanding the attributes that govern the activity of this novel antimicrobial system, we compared the functional and mechanistic properties of a known octamer and a newly generated hexamer analog. The data provide strong evidence for multiple similarities that included high tissue stability, low hemolysis, large-spectrum antibacterial activity in vitro, and the ability to prevent Escherichia coli-induced mortality in vivo. Despite these similarities, however, the octamer mode of action involved membrane disruption, unlike the hexamer, which acted predominantly through inhibition of DNA functions with characteristically slower bactericidal kinetics. Collectively, the data support the view that the analogous OAKs induced bacterial death by distinct mechanisms and further suggest that relatively minor differences in the sequence of host defense peptides are responsible for selecting one mechanism over another, possibly in conjunction with differential binding affinities to the external and/or cytoplasmic membrane.

Original languageEnglish
Pages (from-to)2652-2661
Number of pages10
JournalFASEB Journal
Issue number8
StatePublished - Aug 2008
Externally publishedYes


  • Host defense peptides
  • Intracellular targets
  • Mechanism of action
  • Peptidomimetics


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