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Gewählte Publikation:

Hollaus, R; Ittig, S; Hofinger, A; Haegman, M; Beyaert, R; Kosma, P; Zamyatina, A; .
(2015): Chemical Synthesis of Burkholderia Lipid A Modified with Glycosyl Phosphodiester-Linked 4-Amino-4-deoxy-β-L-arabinose and Its Immunomodulatory Potential.
Chemistry. 2015; 21(10):4102-4114 FullText FullText_BOKU

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-beta-L-arabinose (beta-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 beta-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 beta-L-Ara4N H-phosphonate to a-lactol of beta(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, beta-L-Ara4N-substituted Burkholderia Lipid A. The beta-L-Ara4N modification significantly enhanced the pro-inflammatory innate immune signaling of otherwise non-endotoxic Burkholderia Lipid A.
Autor*innen der BOKU Wien:
Hofinger-Horvath Andreas
Hollaus Ralph
Kosma Paul
Zamyatina Alla
BOKU Gendermonitor:

Find related publications in this database (Keywords)
glycosyl phosphates
structure-activity relationships

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