Polyoxometalate Clusters Integrated into Peptide Chains and as Inorganic Amino Acids: Solution- and Solid-Phase Approaches

General synthetic methods for the grafting of peptide chains onto polyoxometalate clusters by the use of general activated precursors have been developed. Using a solution‐phase approach, pre‐synthesized peptides can be grafted to a metal oxide cluster to produce hybrids of unprecedented scale (up to 30 residues). An adapted solid‐phase method allows the incorporation of these clusters, which may be regarded as novel hybrid unnatural amino acids, during the peptide synthesis itself. These methods may open the way for the automated synthesis of peptides and perhaps even proteins that contain “inorganic” amino acids. Pepping up POMs: The incorporation of polyoxometalates (POMs) into peptides was realized by the use of activated precursors. Using a solution‐phase approach, pre‐synthesized peptides can be grafted onto the metal oxide cluster to produce hybrids of unprecedented scale. An adapted solid‐phase method allows direct incorporation of these clusters during peptide synthesis as hybrid unnatural amino acids.