Synthesis of the Core Structure of the Lipoteichoic Acid of Streptococcus pneumoniae

Christian Marcus Pedersen; Ignacio Figueroa-Perez; Joshodeep Boruwa; Buko  Lindner; Artur J.  Ulmer; Ulrich  Zähringer; Richard R.  Schmidt

doi:10.1002/chem.201001204

Synthesis of the Core Structure of the Lipoteichoic Acid of Streptococcus pneumoniae

Christian Marcus Pedersen, Ignacio Figueroa-Perez, Joshodeep Boruwa, Buko Lindner, Artur J. Ulmer, Ulrich Zähringer, Richard R. Schmidt

26 Citations (Scopus)

Abstract

Streptococcus pneumoniae LTA is a highly complex glycophospholipid that consists of nine carbohydrate residues: three glucose, two galactosamine and two 2-acetamino-4-amino-2,4,6-trideoxygalactose (AATDgal) residues that are each differently linked, one ribitol and one diacylated glycerol (DAG) residue. Suitable building blocks for the glucose and the AATDgal residues were designed and their synthesis is described in this paper. These building blocks permitted the successful synthesis of the core structure Glcβ(1-3)AATDgalβ(1-3) Glcα(1-O)DAG in a suitably protected form for further chain extension (1b, 1c) and as unprotected glycolipid (1a) that was employed in biological studies. These studies revealed that 1a as well as 1 lead to interleukin-8 release, however not via TLR2 or TLR4 as receptor. The core: The synthesized core structure (1) of S. pneumoniae LTA (lipoteichoic acid) exhibited similar stimulation of interleukin-8 release as the recently synthesized complete LTA consisting of the core structure and the pseudopentasaccharidic repeating unit. Contrary to previous postulations, TLR2 is not the signalling receptor for these compounds.

Original language	Danish
Journal	Chemistry: A European Journal
Volume	16
Issue number	42
Pages (from-to)	12627-12641
ISSN	0947-6539
DOIs	https://doi.org/10.1002/chem.201001204
Publication status	Published - 8 Nov 2010
Externally published	Yes

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title = "Synthesis of the Core Structure of the Lipoteichoic Acid of Streptococcus pneumoniae",

abstract = "Streptococcus pneumoniae LTA is a highly complex glycophospholipid that consists of nine carbohydrate residues: three glucose, two galactosamine and two 2-acetamino-4-amino-2,4,6-trideoxygalactose (AATDgal) residues that are each differently linked, one ribitol and one diacylated glycerol (DAG) residue. Suitable building blocks for the glucose and the AATDgal residues were designed and their synthesis is described in this paper. These building blocks permitted the successful synthesis of the core structure Glcβ(1-3)AATDgalβ(1-3) Glcα(1-O)DAG in a suitably protected form for further chain extension (1b, 1c) and as unprotected glycolipid (1a) that was employed in biological studies. These studies revealed that 1a as well as 1 lead to interleukin-8 release, however not via TLR2 or TLR4 as receptor. The core: The synthesized core structure (1) of S. pneumoniae LTA (lipoteichoic acid) exhibited similar stimulation of interleukin-8 release as the recently synthesized complete LTA consisting of the core structure and the pseudopentasaccharidic repeating unit. Contrary to previous postulations, TLR2 is not the signalling receptor for these compounds.",

author = "Pedersen, {Christian Marcus} and Ignacio Figueroa-Perez and Joshodeep Boruwa and Buko Lindner and Ulmer, {Artur J.} and Ulrich Z{\"a}hringer and Schmidt, {Richard R.}",

year = "2010",

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AU - Pedersen, Christian Marcus

AU - Figueroa-Perez, Ignacio

AU - Boruwa, Joshodeep

AU - Lindner, Buko

AU - Ulmer, Artur J.

AU - Zähringer, Ulrich

AU - Schmidt, Richard R.

PY - 2010/11/8

Y1 - 2010/11/8

N2 - Streptococcus pneumoniae LTA is a highly complex glycophospholipid that consists of nine carbohydrate residues: three glucose, two galactosamine and two 2-acetamino-4-amino-2,4,6-trideoxygalactose (AATDgal) residues that are each differently linked, one ribitol and one diacylated glycerol (DAG) residue. Suitable building blocks for the glucose and the AATDgal residues were designed and their synthesis is described in this paper. These building blocks permitted the successful synthesis of the core structure Glcβ(1-3)AATDgalβ(1-3) Glcα(1-O)DAG in a suitably protected form for further chain extension (1b, 1c) and as unprotected glycolipid (1a) that was employed in biological studies. These studies revealed that 1a as well as 1 lead to interleukin-8 release, however not via TLR2 or TLR4 as receptor. The core: The synthesized core structure (1) of S. pneumoniae LTA (lipoteichoic acid) exhibited similar stimulation of interleukin-8 release as the recently synthesized complete LTA consisting of the core structure and the pseudopentasaccharidic repeating unit. Contrary to previous postulations, TLR2 is not the signalling receptor for these compounds.

AB - Streptococcus pneumoniae LTA is a highly complex glycophospholipid that consists of nine carbohydrate residues: three glucose, two galactosamine and two 2-acetamino-4-amino-2,4,6-trideoxygalactose (AATDgal) residues that are each differently linked, one ribitol and one diacylated glycerol (DAG) residue. Suitable building blocks for the glucose and the AATDgal residues were designed and their synthesis is described in this paper. These building blocks permitted the successful synthesis of the core structure Glcβ(1-3)AATDgalβ(1-3) Glcα(1-O)DAG in a suitably protected form for further chain extension (1b, 1c) and as unprotected glycolipid (1a) that was employed in biological studies. These studies revealed that 1a as well as 1 lead to interleukin-8 release, however not via TLR2 or TLR4 as receptor. The core: The synthesized core structure (1) of S. pneumoniae LTA (lipoteichoic acid) exhibited similar stimulation of interleukin-8 release as the recently synthesized complete LTA consisting of the core structure and the pseudopentasaccharidic repeating unit. Contrary to previous postulations, TLR2 is not the signalling receptor for these compounds.

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