We present here a general and straightforward chemoenzymatic method for synthesis of well-defined protein dendrimers. The method involves a simple two-step process in which proteins appended with an orthogonal label by facile sortase-mediated ligation are conjugated to a multivalent dendritic scaffold using the versatile copper-catalyzed azide-alkyne cycloaddition reaction. The ‘Sortase-Click’ strategy produces satisfactory yield of dendrimers under mild conditions from readily available His6-tagged proteins and serves as a powerful general strategy for covalent assembly of protein dendrimers.
