Digestion, fermentation, and pathogen anti-adhesive properties of the hMO-mimic di-fucosyl-ß-cyclodextrin.

Human milk is widely acknowledged as the best food for infants, and that is not just because of nutritional features. Human milk also contains a plethora of bioactive molecules, including a large set of human milk oligosaccharides (hMOs). Especially fucosylated hMOs have received attention for their anti-adhesive effects on pathogens, preventing attachment to the intestine and infection. Because hMOs are generally challenging to produce in sufficient quantities to study and ultimately apply in (medical) infant formula, novel compounds that are inspired by hMO structures (so-called "mimics") are interesting compounds to produce and evaluate for their biological effects. Here we present our thorough study into the digestion, fermentation and anti-adhesive capacity of the novel compound di-fucosyl-ß-cyclodextrin (DFßCD), which was inspired by the molecular structures of hMOs. We establish that DFßCD is not digested by α-amylase and also resistant to fermentation by microbial enzymes from a 9 month-old infant inoculum. In addition, we reveal that DFßCD blocks adhesion of enterotoxigenic E. coli (ETEC) to Caco-2 cells, especially when DFßCD is pre-incubated with ETEC prior to addition to the Caco-2 cells. This suggests that DFßCD functions through a decoy effect. We expect that our results inspire the generation and biological evaluation of other fucosylated hMOs and mimics, to obtain a comprehensive overview of the anti-adhesive power of fucosylated glycans.

Direct and Regioselective Di-α-fucosylation on the Secondary Rim of ß-Cyclodextrin.

A straightforward glycosylation method is described to regio- and stereoselectively introduce two α-l-fucose moieties directly to the secondary rim of ß-cyclodextrin. Using NMR and MS fragmentation studies, the nonasaccharide structure was determined, which was also visualized using molecular dynamics simulations. The reported glycosylation method proved to be robust on gram-scale, and may be generally applied to directly glycosylate ß-cyclodextrins to make well-defined multivalent glycoclusters.

Pyranoside-into-furanoside rearrangement: new reaction in carbohydrate chemistry and its application in oligosaccharide synthesis.

Great interest in natural furanoside-containing compounds has challenged the development of preparative methods for their synthesis. Herein a novel reaction in carbohydrate chemistry, namely a pyranoside-into-furanoside (PIF) rearrangement permitting the transformation of selectively O-substituted pyranosides into the corresponding furanosides is reported. The discovered process includes acid-promoted sulfation accompanied by rearrangement of the pyranoside ring into a furanoside ring followed by solvolytic O-desulfation. This process, which has no analogy in organic chemistry, was shown to be a very useful tool for the synthesis of furanoside-containing complex oligosaccharides, which was demonstrated by synthesizing disaccharide derivatives α-D-Galp-(1→3)-ß-D-Galf-OPr, 3-O-s-lactyl-ß-D-Galf-(1→3)-ß-D-Glcp-OPr, and α-L-Fucf-(1→4)-ß-D-GlcpA-OPr related to polysaccharides from the bacteria Klebsiella pneumoniae and Enterococcus faecalis and the brown seaweed Chordaria flagelliformis.