Synthesis of Cholesterol-Substituted Glycopeptides for Tailor-Made Glycocalyxification of Artificial Membrane Systems

Synthetic minimal membrane systems are extremely useful for better understanding of complex cellular structures and cell surface processes. We have developed a facile method for synthesis of cholesterylated peptides, each bearing a carbohydrate moiety and a fluorescent tag. The position of the cholesterol moiety on the peptide can be controlled by using a new Fmoc-protected cholesterol-triazole-lysine group, which we constructed by means of solid-phase peptide synthesis. We succeeded in integrating the glyco modules into giant unilamellar vesicles by electroformation or infusion in buffer solution. The glyco-decorated liposomes were recognized by a lectin and had unique topological membrane features. In conclusion, this work is a proof of principle for the functionalization of artificial membranes with a primitive synthetic glycocalyx useful for studying carbohydrate-protein interactions on a simplified cell-like membrane surface.