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Synthesis of 6-PEtN...
Synthesis of 6-PEtN-alpha-D-GalpNAc-(1 -> 6)-beta-D-Galp-( 1 -> 4)-beta-D-GlcpNAc-(1 -> 3)-beta-D-Galp-(1 -> 4)-beta-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof
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- Sundgren, Andreas (author)
- Gothenburg Univ, Dept Chem, S-41296 Gothenburg, Sweden.
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- Lahmann, Martina (author)
- Univ Bangor, Sch Chem, Bangor LL57 2UW, Gwynedd, Wales.
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- Oscarson, Stefan (author)
- Natl Univ Ireland Univ Coll Dublin, Ctr Synth & Chem Biol, Dublin 4, Ireland.
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Gothenburg Univ, Dept Chem, S-41296 Gothenburg, Sweden Univ Bangor, Sch Chem, Bangor LL57 2UW, Gwynedd, Wales. (creator_code:org_t)
- 2010-07-26
- 2010
- English.
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In: Beilstein Journal of Organic Chemistry. - : Beilstein Institut. - 2195-951X .- 1860-5397. ; 6, s. 704-708
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Abstract
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- Background: In bacteria with truncated lipopolysaccharide structures, i.e., lacking the O-antigen polysaccharide part, core structures are exposed to the immune system upon infection and thus their use as carbohydrate surface antigens in glycoconjugate vaccines can be considered and investigated. One such suggested structure from Haemophilus influenzae LPS is the phosphorylated pentasaccharide 6-PEtN-alpha-D-GalpNAc-(1 -> 6)-beta-D-Galp-(1 -> 4)-beta-D-GlcpNAc-(1 -> 3)-beta-D-Galp-(1 -> 4)-beta-D-Glcp. Results: Starting from a spacer-containing lactose derivative a suitably protected lacto-N-neotetraose tetrasaccharide structure was constructed through subsequential couplings with two thioglycoside donors, a glucosamine residue followed by a galactose derivative, using NIS/AgOTf as promoter. Removal of a silyl protecting group at the primary position of the non-reducing end residue afforded an acceptor to which the terminal a-galactosamine moiety was introduced using a 2-azido bromo sugar and halide assisted coupling conditions. Global deprotection afforded the non-phosphorylated target pentasaccharide, whereas removal of a silyl group from the primary position of the non-reducing end residue produced a free hydroxy group which was phosphorylated using H-phosphonate chemistry to yield the phosphoethanolamine-containing protected pentasaccharide. Partial deprotection afforded the phosphorylated target pentasaccharide with a free spacer amino group but with a protected phosphoethanolamino group. Conjugation of the spacer amino group to biotin or dimethyl squarate followed by deprotection of the phosphoethanolamino group and, in the case of the squarate derivative, further reaction with a protein then afforded the title conjugates. Conclusion: An effective synthesis of a biologically interesting pentasaccharide structure has been accomplished. The target pentasaccharide, an alpha-GalNAc substituted lacto-N-neotetraose structure, comprises a phosphoethanolamine motif and a spacer aglycon. Through the spacer, biotin and protein conjugates of the title compound have been constructed to allow further use in biological experiments.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- conjugate vaccines
- glycoconjugates
- Haemophilus influenzae
- lacto-N-neotetraose
- oligosaccharide synthesis
- thioglycosides
Publication and Content Type
- ref (subject category)
- art (subject category)
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