Assembly of π-Conjugated Helical Peptides into a Porous and Evolvable Protein-like Lattice

The evolution of proteins from simpler, self-assembled peptides provides a powerful blueprint for the design of complex synthetic mate-rials. Previously, peptide–metal frameworks using short sequences (≤ 3 residues) have shown great promise as proteomimetic materials that exhibit sophisticated capabilities. However, their evolution has been hindered due to few mutable residues and restricted choice of side-chains that are compatible with metal ions. Herein, we developed a non-covalent strategy using π-stacking to assemble much longer peptides into crystalline frameworks that tolerate even previously incompatible acidic and basic functionalities, and allow an unprecedent-ed level of pore mutations. Single-crystal X-ray structures are provided for all mutants to guide and validate rational design. These materi-als exhibit hallmark protein behaviors such as guest-selective induced-fit and assembly of multi-metallic units. Significantly, we demon-strate facile evolution of the framework to substantially increase affinity towards a complex organic molecule.