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Gewählte Publikation:

Zamyatina, A; Hollaus, R; Blaukopf, M; Kosma, P.
(2012): Synthesis of lipid A and inner-core lipopolysaccharide (LPS) ligands containing 4-amino-4-deoxy-L-arabinose units
PURE APPL CHEM. 2012; 84(1): 11-21. FullText FullText_BOKU

Abstract:
Attachment of 4-amino-4-deoxy-L-arabinose (Ara4N) to phosphates or sugar hydroxyl groups of lipopolysaccharide (LPS) contributes to bacterial resistance against common antibiotics. For a detailed study of antigenic properties and binding interactions, Ara4N-containing inner-core ligands related to Burkholderia and Proteus LPS have been synthesized in good yields. Glycosylation at position 8 of allyl glycosides of oct-2-ulosonic acids (Ko, Kdo) has been accomplished using an N-phenyltrifluoroacetimidate 4-azido-4-deoxy-L-arabinosyl glycosyl donor followed by azide reduction and global deprotection. The beta-L-Ara4N-(1 -> 8)-alpha-Kdo disaccharide was further extended into the branched beta-L-Ara4N-(1 -> 8)[alpha-Kdo-(2 -> 4)]-alpha-Kdo trisaccharide via a regioselective glycosylation of a protected triol intermediate. Synthesis of Ara4N-modified lipid A part structure occurring in the LPS of Burkholderia, Pseudomonas, and Klebsiellla strains was accomplished using the H-phosphonate approach. The stereocontrolled assembly of the phosphodiester linkage connecting glycosidic centers of two aminosugars was elaborated employing an anomeric H-phosphonate of cyclic silyl-ether protected 4-azido-4-deoxy-beta-L-arabinose, which was coupled to the hemiacetal of the lipid A GlcN-disaccharide backbone. Conditions for global deprotection, which warrant the integrity of "double anomeric" phosphodiester linkage, were successfully developed. Introduction of thiol-terminated spacer at the synthetic ligands allows both coupling to bovine serum albumin (BSA) and immobilization on gold nano particles as well as generation of glycoarrays.
Autor*innen der BOKU Wien:
Blaukopf Markus
Hollaus Ralph
Kosma Paul
Zamyatina Alla
BOKU Gendermonitor:


Find related publications in this database (Keywords)
antimicrobial activity
carbohydrates
endotoxins
Kdo
lipid A
lipopolysaccharide
organic synthesis
phosphodiesters


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