DNA-Templated Assembly of Metalloprotein Mimics with Hydrolytic Activity

Metalloproteins perform a wide range of biological and chemical functions, but elucidating their sequence-function relationships is difficult due to their complex folding pathways and various interactions involved. In this study, we use a covalently branched DNA trimer to scaffold the assembly of diverse peptide secondary structures into higher-order metalloprotein mimics. These structures exhibit zinc ion binding and hydrolytic activity, resembling the natural enzyme carbonic anhydrase (CA). By independently addressing each peptide fragment, we constructed a diverse library of protein mimics, enabling a systematic, high-throughput exploration of peptide structure-function relationships. This strategy expands the design potential beyond conventional coiled-coil motifs, offering a powerful methodology for constructing functional protein-based architectures.