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Deuterium-labelled N-acyl-l-homoserine lactones (AHLs)—inter-kingdom signalling molecules—synthesis, structural studies, and interactions with model lipid membranes

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Abstract

N-Acyl-l-homoserine lactones (AHLs) are synthesized by Gram-negative bacteria. These quorum-sensing molecules play an important role in the context of bacterial infection and biofilm formation. They also allow communication between microorganisms and eukaryotic cells (inter-kingdom signalling). However, very little is known about the entire mechanism of those interactions. Precise structural studies are required to analyse the different AHL isomers as only one form is biologically most active. Theoretical studies combined with experimental infrared and Raman spectroscopic data are therefore undertaken to characterise the obtained compounds. To mimic interactions between AHL and cell membranes, we studied the insertion of AHL in supported lipid bilayers, using vibrational sum-frequency-generation spectroscopy. Deuterium-labelled AHLs were thus synthesized. Starting from readily available deuterated fatty acids, a two-step procedure towards deuterated N-acyl-l-homoserine lactones with varying chain lengths is described. This included the acylation of Meldrum’s acid followed by amidation. Additionally, the detailed analytical evaluation of the products is presented herein.

Figure Deuterium labelled N-acyl-l-homoserine lactones (AHLs) were synthesized in 2 steps. The combination of theoretical and experimental IR and Raman spectroscopy enables identification of most probable structures of AHLs. The integration of the deuterated AHLs in model lipid membranes (supported lipid bilayers) was further investigated using sum-frequency-generation (SFG) spectroscopy, to mimic interactions between AHL and cell membranes

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Abbreviations

3OC8-d 9-HSL:

N-(3-Oxooctanoyl-d 9)-l-homoserine lactone

3OC12-d 17-HSL:

N-(3-Oxododecanoyl-d 17)-l-homoserine lactone

3OC14-d 21-HSL:

N-(3-Oxotetradecanoyl-d 21)-l-homoserine lactone

AHLs:

N-Acyl-l-homoserine lactones

DFT:

Density functional theory

ESI-TOF MS:

Electrospray ionization time-of-flight mass spectrometry

ESI-MS/MS:

Electrospray ionization tandem mass spectrometry

HRMS:

High-resolution mass spectrometry

IR:

Infrared spectroscopy

QCM-D:

Quartz crystal microbalance with dissipation

SFG:

Sum-frequency-generation

SLBs:

Supported lipid bilayers

TLC:

Thin-layer chromatography

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Acknowledgements

Financial support from the Helmholtz program Bio-interfaces is gratefully acknowledged. A.K. and K.F. were supported by the DFG-funded transregional collaborative research centre SFB/TRR 88 “3MET”. We thank Stefan Heissler from Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces (IFG) for help with IR and Raman spectra acquisition. P.K. and C.B. thank Sofia Svedhem from Chalmers University of Technology for help with QCM-D and SLB preparation as well as Michael Grunze for his support.

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Authors and Affiliations

  1. Karlsruhe Institute of Technology, Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany

    Dorota Jakubczyk & Stefan Bräse

  2. Karlsruhe Institute of Technology, Institute of Functional Interfaces, Hermann von Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany

    Dorota Jakubczyk & Gerald Brenner-Weiß

  3. Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Hermann von Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany

    Christoph Barth, Frances Anastassacos, Patrick Koelsch & Ute Schepers

  4. Karlsruhe Institute of Technology, Institute of Nanotechnology, Hermann von Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany

    Adam Kubas & Karin Fink

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  1. Dorota Jakubczyk
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Correspondence to Gerald Brenner-Weiß or Stefan Bräse.

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Jakubczyk, D., Barth, C., Kubas, A. et al. Deuterium-labelled N-acyl-l-homoserine lactones (AHLs)—inter-kingdom signalling molecules—synthesis, structural studies, and interactions with model lipid membranes. Anal Bioanal Chem 403, 473–482 (2012). https://doi.org/10.1007/s00216-012-5839-4

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  • DOI: https://doi.org/10.1007/s00216-012-5839-4

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