Metal-α-Helix Peptide Frameworks.

Metal-peptide frameworks (MPFs) are a growing class of metal-organic frameworks with promising applications in metalloprotein mimicry, chiral separations, and catalysis. There are limited examples of MPFs, especially those with both secondary structure and natural amino acid side chains that coordinate to metal nodes, which are important for accurately mimicking metalloprotein active sites. Here, we design a robust and modular strategy based on short α-helical peptides (nine amino acids long) to form frameworks with many types of biomimetic metal sites. Peptides were designed to have Glu and His metal-binding residues, hydrophobic residues, and noncanonical helix-enforcing residues. With Co(II), it was shown that mutagenesis of a single amino acid near the metal-binding residues generates a diverse library of frameworks with varying metal node coordination geometries and compositions. Structures for 16 out of 20 variants were characterized by single-crystal X-ray diffraction, revealing how noncovalent interactions impact the metal primary sphere. In one case, a point mutation turns on reversible ligand-triggered conformational changes, demonstrating that this platform allows for dynamic behavior like that observed in metalloproteins. Furthermore, we show that frameworks readily assemble with Mn(II), Fe(II), Cu(II), and Zn(II) ions, highlighting the generality of this approach. The ease-of-synthesis, modularity, and crystallinity of these materials make this a highly accessible platform for studying and engineering biomimetic metal centers in porous materials.