Non-covalent synthesis of a multivalent enzyme

We report the synthesis of a non-covalent protein dendrimer using the strong and highly specific interaction between S-peptide and S-protein. Assocn. of S-peptide and S-protein results in the formation of an active enzyme, RNase S, whereas neither fragment alone displays any enzyme activity. Native chem. ligation was used to couple four S-peptides via their C-terminal thioester to a cysteine-functionalized synthetic scaffold to yield a tetravalent S-peptide dendrimer. A fully functional RNase S tetramer was prepd. by addn. of four equiv. of S-protein. Complex formation was studied using a fluorescent enzyme activity assay and mass spectrometry. This new strategy towards multivalent proteins can be used to synthesize complex semi-synthetic protein assemblies, which may find applications in nanomedicine or functional biomaterials. [on SciFinder (R)]