TY - JOUR
T1 - Impact of self-assembly properties on antibacterial activity of short acyl-lysine oligomers
AU - Sarig, Hadar
AU - Rotem, Shahar
AU - Ziserman, Lior
AU - Danino, Dganit
AU - Mor, Amram
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/12
Y1 - 2008/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=57049123894&partnerID=8YFLogxK
U2 - 10.1128/AAC.00656-08
DO - 10.1128/AAC.00656-08
M3 - 文章
C2 - 18838600
AN - SCOPUS:57049123894
VL - 52
SP - 4308
EP - 4314
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 12
ER -