Definition of Structural Prerequisites for Lipoteichoic Acid-Inducible Cytokine Induction by Synthetic Derivatives

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2003
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Deininger, Susanne
Stadelmaier, Andreas
Morath, Siegfried
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The Journal of Immunology. 2003, 170(8), pp. 4134-4138. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/jimmunol.170.8.4134
Zusammenfassung

The controversy about the immune stimulatory properties of lipoteichoic acid (LTA) from Staphylococcus aureus was solved recently by showing decomposition and inactivation of LTA obtained by conventional purification strategies, as well as pronounced LPS contamination of commercial preparations. By introducing a novel preparation method, the structure of bioactive LTA was elucidated. This structure was confirmed by chemical synthesis. In this work, synthetic LTA derivatives were employed to study the structure-function relationship of cytokine induction in human monocytes. Synthetic LTA induced the same cytokine pattern as highly purified natural LTA. The gentiobiose core could be omitted without affecting bioactivity. The polyglycerophosphate backbone amplified the response to the lipid anchor (~100-fold) only when substituted with D-alanine, whereas α-D-N-acetylglucosamine substituents could be omitted. Replacing D-alanine substituents with L-alanine reduced the activity of the molecule at least 10-fold, indicating stereoselectivity. These results define for the first time the crucial patterns required for the immune recognition of LTA.

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570 Biowissenschaften, Biologie
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ISO 690DEININGER, Susanne, Andreas STADELMAIER, Sonja von AULOCK, Siegfried MORATH, Richard R. SCHMIDT, Thomas HARTUNG, 2003. Definition of Structural Prerequisites for Lipoteichoic Acid-Inducible Cytokine Induction by Synthetic Derivatives. In: The Journal of Immunology. 2003, 170(8), pp. 4134-4138. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/jimmunol.170.8.4134
BibTex
@article{Deininger2003Defin-6619,
  year={2003},
  doi={10.4049/jimmunol.170.8.4134},
  title={Definition of Structural Prerequisites for Lipoteichoic Acid-Inducible Cytokine Induction by Synthetic Derivatives},
  number={8},
  volume={170},
  issn={0022-1767},
  journal={The Journal of Immunology},
  pages={4134--4138},
  author={Deininger, Susanne and Stadelmaier, Andreas and Aulock, Sonja von and Morath, Siegfried and Schmidt, Richard R. and Hartung, Thomas}
}
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