Copper-containing metalloenzymes constitute a major class of proteins which catalyze a vast number of reactions in nature. Inspired by the structural and functional characteristics of this unique class of metalloenzymes, we will describe the conception, design, characterization, and catalytic studies of de novo designed artificial copper peptides (ArCuPs) that activate small molecules such as peroxide, dioxygen, and the C-H bonds of hydrocarbons. Using a first principles approach, the ArCuPs are designed to coordinate one Cu via homoleptic His residues introduced at an a site of the peptide heptad. X-ray crystallographic, UV-vis, EPR, and protein-film electrochemistry are used to determine the coordination and redox properties of the ArCuPs in the absence and presence of the substrates. A reductive priming step accelerates the rate of reactions. Detailed characterization of the catalytic behavior of the ArCuPs led us to determine the catalytic parameters (KM, kcat, TON) and establish the peroxidase/oxidase/oxygenase activity of the ArCuPs.

Designer metallopeptides for small molecule activation

ACS Fall 2021

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