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Chemical synthesis of Burkholderia Lipid A modified with glycosyl phosphodiester-linked 4-amino-4-deoxy-β-L-arabinose and its immunomodulatory potential

Hollaus, Ralph and Ittig, Simon Josef and Hofinger, Andreas and Haegman, Mira and Beyaert, Rudi and Kosma, Paul and Zamyatina, Alla. (2015) Chemical synthesis of Burkholderia Lipid A modified with glycosyl phosphodiester-linked 4-amino-4-deoxy-β-L-arabinose and its immunomodulatory potential. Chemistry, a European journal, 21 (10). pp. 4102-4114.

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Official URL: http://edoc.unibas.ch/39982/

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Abstract

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 α-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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Ittig, Simon Josef
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley-VCH Verlag
ISSN:0947-6539
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:30 Jun 2016 11:00
Deposited On:30 May 2016 08:46

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