Application of β-1,4-galactosyltransferase in the synthesis of complex branched-chain oligosaccharide mimics of fragments of the capsular polysaccharide of Streptococcus pneumoniae type 14

Abstract

The chemoenzymic synthesis is described of β-D-Galp-(1→4)-β-D-Glcp-(1→6)-[β-D-Galp-(1→4)]-β-D-GlcpNAc-(1→O[CH₂]₃O→4)-β-D-Glcp-(1→OCH₂CHCH₂) 32 and β-D-Galp-(1→4)-β-D-GlcpNAc-(1→ O[CH₂]₃O→4)-β-D-Glcp-(1→6)-[β-D-Galp-(1→4)]-β-D-GlcpNAc-(1→O[CH₂]₃O→4)-β-D-Glcp-(1→OCH₂- CHCH₂) 33, representing hexa- and octasaccharide mimics of fragments of the Streptococcus pneumoniae type 14 polysaccharide. In a chemical approach the intermediate linear oligosaccharide mimics 30 and 31 were synthesized, wherein both terminal and non-terminal N-acetyl-β-D-glucosamine residues were not yet galactosylated. The alkyl-bridged derivatives were found to be good acceptor substrates for bovine milk β-1,4-galactosyltransferase. Reaction of the anomeric allyl functions with cysteamine under UV-irradiation gave the corresponding 3-(2-aminoethylthio)propyl glycosides 34 and 35, suitable for further coupling of the oligosaccharide mimics to protein carriers.