Synthesis of a Lewis b hexasaccharide thioglycoside donor and its use towards an extended mucin core Tn heptasaccharide structure and a photoreactive biotinylated serine linked hexasaccharide

Abstract

Investigation into Heliobacter pylori binding to Lewis b (Le^b) antigens through the blood group antigen binding adhesion protein (BabA) requires structurally well-defined tools. A Le^b hexasaccharide thioglycoside donor was chemically prepared through a linear approach starting from D-lactose. This donor can be used to attach reducing end linkers providing a range of options for conjugation techniques or to further extend the oligosaccharide structure. To evaluate its efficiency as a donor, it was coupled to a 6-OH GalNAc acceptor, producing an extended Le^b-containing Tn mucin core structure in 84% yield, and to L-serine in 72% yield. The latter compound was subsequently functionalized with a photolabile diazirine linker and biotin, creating a Le^b hexasaccharide structure–function tool suitable for lectin tagging interaction studies. This donor opens a wide range of possibilities for conjugation of Le^b structures to produce a variety of chemical biology tools to assist in the study of these interactions.