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.