Abstract
Peptideโbased metalloprotein models represent useful systems to help understand how metalloproteins can support different functions, by the use of similar metal ion cofactors. In order to shed light on the role of the protein matrix in modulating the heme properties, we developed new models: mimochromes. They are pseudoโC~2~ symmetric systems, composed of two helical peptides covalently linked to the deuteroporphyrin. The use of C~2~ symmetry is particularly advantageous, because it simplifies the design, synthesis and characterization. However, it leaves the problem of possible diastereomeric forms. In the cobalt complex of the first derivative, mimochrome I, ฮ and ฮ isomers were indeed experimentally observed. All the insights derived from the Co^III^โmimochrome I structure were used to obtain a reโdesigned molecule, mimochrome IV. The spectroscopic characterization of the iron and cobalt derivatives suggested the presence of the ฮ isomer as unique species. The NMR solution structure of the diamagnetic Co^III^โmimochrome IV confirmed the ability of the molecule to adopt a unique topology, and revealed the peptide chains to be in helical conformation, as designed. The insertion of intramolecular, interโchain interactions was successful in favoring the formation of one of the two possible diastereomers. The stereochemically stable structure of mimochrome IV provides an attractive model for modulating the redox potential of the heme, by simple changing the peptide chain composition around the heme.