Semi-synthetic approaches to probe mucin function

Here we investigate how alterations of the glycosylation patterns and the number of TRs affect the functional properties of mucins. For this purpose, we use a combination of chemical semi-synthesis and purification techniques to extract glycan building blocks from natural sources.

The chemical synthesis of long O-glycopeptides is challenging and requires a combination of linear solid phase synthesis (SPS) and ligation techniques. In the first funding period, we developed powerful ligation auxiliaries that allow ligation reactions to be carried out at virtually any ligation junction. We introduced a glyco-economic synthesis of long, multiglycosylated TRs, solving a key problem: the synthesis of MUC5AC multi-tandem repeat peptides with a high degree of glycosylation matching clustered glycosylation found in nature. This provides the basis for subsequent work focussing on introducing glycans of increased complexity.