Chemical methods to stabilize segments of metalloproteins in the form of peptides.

Importing metalloprotein active sites into simplified systems is needed to better understand the fundamental chemistry of these sites, and it can also enable the fabrication of synthetic materials with biomimetic function. It remains unclear how the unique coordination environments within metalloproteins, composed generally of imidazoles, carboxylates, and water, contribute to the extraordinary reactivity of metalloenzymes. There are limited methods to excise a metalloprotein active site, especially without requiring arduous organic synthesis. We have recently developed a strategy that enables rapid engineering of metalloprotein-like coordination sites based on easy-to-synthesize and modular metal-peptide porous materials. Here, we explain in detail the design, synthesis, and characterization of a metal-peptide framework that closely replicates the structure of the 2His-1carboxylate facial triad motif, a highly conserved ligand environment found in many oxygenases.