Impact of self-assembly properties on antibacterial activity of short acyl-lysine oligomers

Hadar Sarig, Shahar Rotem, Lior Ziserman, Dganit Danino, Amram Mor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

We investigated both the structural and functional consequences of modifying the hydrophobic, lipopeptide-mimetic oligo-acyl-lysine (OAK) N α-hexadecanoyl-L-lysyl-L-lysyl-aminododecanoyl-L-lysyl-amide (c16KKc12K) to its unsaturated analog hexadecenoyl- KKc12K [c16(ω7)KKc12K]. Despite similar tendencies for self-assembly in solution (critical aggregation concentrations, ∼10 μM), the analogous OAKs displayed dissimilar antibacterial properties (e.g., bactericidal kinetics taking minutes versus hours). Diverse experimental evidence provided insight into these discrepancies: whereas c 16(ω7)KKc12K created wiry interconnected nanofiber networks, c16KKc12K formed both wider and stiffer fibers which displayed distinct binding properties to phospholipid membranes. Unsaturation also shifted their gel-to-liquid transition temperatures and altered their light-scattering properties, suggesting the disassembly of c 16(ω7)KKc12K in the presence of bacteria. Collectively, the data indicated that the higher efficiency in interfering with bacterial viability emanated from a wobbly packing imposed by a single double bond. This suggests that similar strategies might improve hydrophobic OAKs and related lipopeptide antibiotics.

Original languageEnglish
Pages (from-to)4308-4314
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume52
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

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