Peptide-based Artificial Metalloenzymes by Design

Peptide engineering has reached impressive results in the last decades. The principles governing folding and stability of peptides and proteins are now well in hand, and advanced tools and strategies for the design of peptide sequences with defined shapes and properties are available. The ability to design complex peptide-based structures has strongly stimulated their application in different fields, such as the development of peptide-based artificial metalloenzymes. Indeed, peptides allow the construction of sufficiently rigid structures for properly positioning the ligands to satisfy the coordination requirements of metal ions. Further, they can be sufficiently flexible to enable housing additional functional groups in proximity of the metal-binding site, which may result important for reactivity. The possibility of inserting unnatural amino acids into peptide sequences has strongly expanded the repertoire of structures/functions achievable with metal-binding peptides. In addition, the design of metal-binding sites into small peptide building blocks can afford metal induced self-assembly and the construction of supramolecular structures. Thanks to all these features, peptide and protein designers have now the possibility of developing customized catalysts, even active in abiotic transformations.