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

Abstract:

: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 (c(16)KKc(12)K) to its unsaturated analog hexadecenoyl-KKc(12)K [c(16(omega7))KKc(12)K]. Despite similar tendencies for self-assembly in solution (critical aggregation concentrations, approximately 10 muM), 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(omega7))KKc(12)K created wiry interconnected nanofiber networks, c(16)KKc(12)K 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(omega7))KKc(12)K 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.

authors

Sarig H,Rotem S,Ziserman L,Danino D,Mor A

doi

10.1128/AAC.00656-08

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

4308-14

issue

12

eissn

0066-4804

issn

1098-6596

pii

AAC.00656-08

journal_volume

52

pub_type

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