Systematic Investigation of Metabolic Oligosaccharide Engineering Efficiency in Intestinal Cells Using a Dibenzocyclooctyne‐Monosaccharide Conjugate

Abstract

AbstractMetabolic oligosaccharide engineering (MOE) of cells with synthetic monosaccharides can introduce functionality to the glycans of cell membranes. Unnatural sugars (e. g., peracetylated mannose‐azide) can be expressed on the cell surface with the azide group in place. After MOE, the azide group can participate in a copper‐free click reaction with an alkyne (e. g., dibenzocyclooctyne, DBCO) probe. This allows the metabolic fate of monosaccharides in cells to be understood. However, in a drug delivery context it is desirable to have azide groups on the probe (e. g. a drug delivery particle) and the alkyne (e. g. DBCO) on the cell surface. Consequently, the labelling efficiency of intestinal cell lines (Caco‐2 and HT29‐MTX‐E12) treated with N‐dibenzocyclooctyne‐tetra‐acetylmannosamine, and the concentration‐ and time‐dependent labelling were determined. Furthermore, the labelling of mucus in HT29‐MTX‐E12 cells with DBCO was shown. This study highlights the potential for using MOE to target azide‐functionalised probes to intestinal tissues for drug delivery applications.