Synthesis of the Lewis b hexasaccharide and squarate acid-HSA conjugates thereof with various saccharide loadings.
The Lewis b hexasaccharide, alpha-L-Fucp-(1 --> 2)-beta-D-Galp-(1 --> 3)-[alpha-L-Fucp-(1 --> 4)]-beta-D-GlcpNAc-(1 --> 3)-beta-D-Galp-(l --> 4)-beta-D-Glcp, has been synthesised using a convergent synthesis. Starting from ethyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside, a thioglycoside tetrasaccharide donor block, was constructed through two orthogonal glycosylations with glycosyl bromide donors. First, the galactose moiety was introduced using silver triflate as a promoter and then the two fucose residues under halide-assisted conditions. Finally, this tetrasaccharide was linked to a spacer-equipped 3I,4I-diol lactose acceptor in a DMTST-promoted coupling to give, after deprotection, the Lewis b hexasaccharide as its 2-aminoethyl spacer-equipped derivative. This was coupled to human serum albumin (HSA), using the squarate ester methodology, in various saccharide-protein ratios, to give neoglycoconjugates with different saccharide loadings in about 50%) efficiency.
Chernyak
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A
Department of Organic Chemistry, University of Stockholm, Sweden.
Oscarson
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S
Turek
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D
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003503:Cyclobutanes / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D006001:Glycoconjugates / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013865:Thioglycosides / Q000737:chemistry
D003503:Cyclobutanes; D004952:Esters; D006001:Glycoconjugates; D009844:Oligosaccharides; D011134:Polysaccharides; D012709:Serum Albumin; D013865:Thioglycosides; C404741:galactopyranosyl-1-3-galactopyranosyl-1-3(4)-N-acetylglucosamine; C030042:squaric acid