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. Indeed, several structural motifs, such as -sheets, / motifs and especially -helices and helical bundles, can presently be designed with highest degree of confidence. The ability to design such peptide-based structures has strongly stimulated their application in different fields, such as the development of peptide-based metalloprotein mimics. 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 enough flexible to enable housing additional functional groups close to the metal binding site that can be important for reactivity. The possibility of inserting non-natural amino acids into the sequences has strongly expanded the repertoire of structure/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 ranging from fibers to micelles. By reviewing the papers appeared in the literature over last two decades, this chapterillustrates the efforts made to reproduce metalloprotein activities in artificial systems, through the use of peptide-based scaffolds. We will describe several metalloprotein mimics organized according to different metal-based prosthetic groups: mononuclear and dinuclear metal-binding sites, as well as hemes and metalloporphyrins.