Total synthesis of lipoteichoic acid of Streptococcus pneumoniae.
نویسندگان
چکیده
Streptococcus pneumoniae is one of the most common Grampositive pathogens. Upon colonizing the upper respiratory tract it causes severe infections and it causes life-threatening diseases like pneumonia, bacteremia, and meningitis when it reaches the lower respiratory tract or the bloodstream,l1J thereby resulting in a high mortality rate,!2·3J As for all Gram-positive bacteria, the cell wall of S. pneumoniae consists of several layers of peptidoglycans, to which teichoic acids are covalently linked, and of lipoteichoic acids (LTAs) which are anchored in the cell membrane. Structural analysis of pneumococcal LTA revealed quite a different chemical composition compared to that of LTA from Staphylococcus aureus.r4J The polyglycerophosphate backbone of staphylococcal LTA is replaced by a pentameric repeating unit which consists of a ribitolphosphate having in some cases an attached GalNAc residue and a tetrasaccharide moiety connected to two attached phosphocholine residues (Scheme 1, 1).[4.5J The pneumococcal LTA is recognized by the innate immune system, thereby stimulating the release of proinflammatory cytokines, but with reduced potency compared to staphylococcal LTA,[6J Activation is supposed to occur through the Toll-like receptor 2 (TLR-2) with CD14 as a coreceptor.[7J However, as TLR-2 appears to recognize a broad range of structurally different bacterial compounds, specific stimulation of the immune system through a TLR-2LTA interaction has been recently questioned.[S-lq In addition, different strains of Gram-positive bacteria produce LTAs having structural variations. Therefore, pneumococcal LTA may have galactose instead of glucose in the repeating unit,[12J ribitol with D-alanine residues,[13. 14J or heterogeneity in the attached phosphocholines.r4J These structural changes may
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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 sy...
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Biological effects of lipoteichoic acids.
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Members of the Mitis group of streptococci possess teichoic acids (TAs) as integral components of their cell wall that are unique among Gram-positive bacteria. Both, lipoteichoic (LTA) and wall teichoic acid, are formed by the same biosynthetic pathway, are of high complexity and contain phosphorylcholine (P-Cho) residues. These residues serve as anchors for choline-binding proteins (CBPs), som...
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عنوان ژورنال:
- Angewandte Chemie
دوره 49 14 شماره
صفحات -
تاریخ انتشار 2010