Click conjugation of trivalent mannosyl glycocluster with human serum albumin to generate a cell targeting delivery vehicle

The exploitation of glycans as targeting agents to construct delivery materials has proved useful for targeted disease diagnosis and therapy. To achieve effective targeting, multivalent glycosides are prepared to enhance avidity with sugar receptors. In this study, we designed and synthesized a new trivalent mannoside (Man₃-PEG₃-N₃) bearing an azido unit. This azido mannosyl glycocluster was used to conjugate with cyclooctyne-modified human serum albumin (HSA) through strain-promoted click chemistry. Mass spectroscopic analysis validated the successful construction of the glycocluster-conjugated HSA, and a fluorescence titration assay indicated that the resulting conjugate is capable of accommodating an environmentally sensitive dye.