metallopeptides

Metallopeptides are chemical species in which a metal ion is coordinated by a peptide or peptide-like ligand. They occur naturally as functional components of metalloproteins and metalloenzymes, and are also prepared synthetically to explore catalysis, signaling, and materials applications.

In metallopeptides, metal binding often involves side chains of histidine, cysteine, aspartate, and glutamate, along with backbone amide nitrogens and bound water. Common motifs include histidine-rich sequences and Cys2His2 zinc-binding arrangements. Metals such as zinc, copper, iron, manganese, cobalt, nickel, and magnesium are encountered. Coordination geometries vary with metal and ligands, including tetrahedral, square planar, and octahedral configurations.

Functions of metallopeptides include structural roles, such as zinc fingers where Zn2+ stabilizes the folded structure; catalytic activity that mimics metalloenzymes; redox capabilities and electron transfer; and sensing or signaling roles where metal binding modulates properties.

Design and synthesis typically involve creating short peptide ligands that present coordinating residues, or incorporating non-natural amino acids to tailor binding. Metal coordination can be induced after assembly, and geometric constraints such as cyclization can improve selectivity and stability. Challenges include controlling the metal oxidation state, competing binding by solvent or other ligands, and achieving high affinity in complex environments.

Applications and research areas encompass biomimetics and catalysis, development of metallopeptide-based catalysts, and metallopeptide sensors and imaging probes, as well as fundamental studies of metal–peptide interactions in biology. Notable examples include zinc-binding motifs in zinc finger domains, which illustrate how peptide scaffolds can orchestrate metal coordination to stabilize structure and function.