Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: cystic fibrosis (CF) [ICD11:
CA25 
];
infection due to Burkholderia [ICD11:
XN01M ]
The structure was elucidated in this paperNCBI PubMed ID: 25630448Publication DOI: 10.1002/chem.201406058Journal NLM ID: 9513783Publisher: Weinheim: VCH Verlagsgesellschaft/Verlag I
Correspondence: alla.zamyatina
boku.ac.at
Institutions: Department of Chemistry, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna (Austria), Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel (Switzerland, Department for Biomedical Molecular Biology, Unit of Molecular Signal Transduction in Inflammation, Ghent University, Inflammation Research Center, VIB, Technologiepark 927, 9052 Ghent (Belgium)
Modification of the Lipid A phosphates by positively charged appendages is a part of the survival strategy of numerous opportunistic Gram-negative bacteria. The phosphate groups of the cystic fibrosis adapted Burkholderia Lipid A are abundantly esterified by 4-amino-4-deoxy-β-L-arabinose (β-L-Ara4N), which imposes resistance to antibiotic treatment and contributes to bacterial virulence. To establish structural features accounting for the unique pro-inflammatory activity of Burkholderia LPS we have synthesised Lipid A substituted by β-L-Ara4N at the anomeric phosphate and its Ara4N-free counterpart. The double glycosyl phosphodiester was assembled by triazolyl-tris-(pyrrolidinyl)phosphonium-assisted coupling of the β-L-Ara4N H-phosphonate to alpha-lactol of β(1→6) diglucosamine, pentaacylated with (R)-(3)-acyloxyacyl- and Alloc-protected (R)-(3)-hydroxyacyl residues. The intermediate 1,1'-glycosyl-H-phosphonate diester was oxidised in anhydrous conditions to provide, after total deprotection, β-L-Ara4N-substituted Burkholderia Lipid A. The β-L-Ara4N modification significantly enhanced the pro-inflammatory innate immune signaling of otherwise non-endotoxic Burkholderia Lipid A.
Lipopolysaccharide, carbohydrates, glycolipids, structure-activity relationships, glycosyl phosphates
Structure type: oligomer
Location inside paper: p.4103, fig.1, p.4106, scheme 4, compound 1
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531,IEDB_176772
Methods: 13C NMR, 1H NMR, TLC, 31P NMR, ESI-MS, chemical synthesis, chemical methods, MALDI-TOF MS, UV, glycosylation
Synthetic data: chemical
NCBI Taxonomy refs (TaxIDs): 32008
Show glycosyltransferases
1H NMR data: present in publication
|
13C NMR data: present in publication
|
There is only one chemically distinct structure:
Found 
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