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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.

Impact of Self-Assembly Properties on Antibacterial Activity of Short Acyl-Lysine Oligomers {triangledown}

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

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{alpha}-hexadecanoyl-L-lysyl-L-lysyl-aminododecanoyl-L-lysyl-amide (c16KKc12K) to its unsaturated analog hexadecenoyl-KKc12K [c16({omega}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({omega}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({omega}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.


* Corresponding author. Mailing address: Laboratory of Antimicrobial Peptides Investigation (LAPI), Department of Biotechnology & Food Engineering, Technion, Haifa 32000, Israel. Phone: (972 4) 8293340. Fax: (972 4) 8293399. E-mail: amor{at}tx.technion.ac.il

{triangledown} Published ahead of print on 6 October 2008.


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.







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