| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Previous Article | Next Article ![]()
Antimicrobial Agents and Chemotherapy, December 2008, p. 4308-4314, Vol. 52, No. 12
0066-4804/08/$08.00+0 doi:10.1128/AAC.00656-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Department of Biotechnology & Food Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
Received 18 May 2008/ Returned for modification 24 July 2008/ Accepted 25 September 2008
We investigated both the structural and functional consequences of modifying the hydrophobic, lipopeptide-mimetic oligo-acyl-lysine (OAK) N
-hexadecanoyl-L-lysyl-L-lysyl-aminododecanoyl-L-lysyl-amide (c16KKc12K) to its unsaturated analog hexadecenoyl-KKc12K [c16(
7)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 c16(
7)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 c16(
7)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.
Published ahead of print on 6 October 2008.
| Clin. Vaccine Immunol. | Clin. Microbiol. Rev. |
|---|---|
| J. Clin. Microbiol. | ALL ASM JOURNALS |