Synthesis of the core structure of the lipoteichoic acid of Streptococcus pneumoniae.
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 (1 b, 1 c) and as unprotected glycolipid (1 a) that was employed in biological studies. These studies revealed that 1 a as well as 1 lead to interleukin-8 release, however not via TLR2 or TLR4 as receptor.
Pedersen
Christian Marcus
CM
Fachbereich Chemie, Universität Konstanz, Fach 725, 78457 Konstanz, Germany.
Figueroa-Perez
Ignacio
I
Boruwa
Joshodeep
J
Lindner
Buko
B
Ulmer
Artur J
AJ
Zähringer
Ulrich
U
Schmidt
Richard R
RR
D006017:Glycolipids / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D016209:Interleukin-8 / Q000097:blood / Q000187:drug effects; D008070:Lipopolysaccharides / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000276:immunology*; D013682:Teichoic Acids / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D006017:Glycolipids; D016209:Interleukin-8; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C009900:lipoteichoic acid