A bioinformatics approach to design minimal biomimetic metal-binding peptides.

Abstract

Nature-inspired or biomimetic catalysts aim to reach the high catalytic performance and selectivity of natural enzymes while possessing the chemical stability and processability of synthetic catalysts. A promising strategy for designing biomimetic catalysts relies on mimicking the structure of the enzyme active site. This can either entail complicated total synthesis of a synthetic catalyst or design of peptide sequences, able to self-assemble in the presence of metal ions, thus forming metallo-peptide complexes that mimic the active sites of natural enzymes. Using a bioinformatics approach, we designed a minimal peptide made up of eight amino acids (H4pep) to act as a functional mimic of the trinuclear Cu site of the laccase enzyme. Cu(II) binding to H4pep results in the formation of a Cu²⁺(H4pep)₂ complex with a β-sheet secondary structure, able to reduce O₂. Our study demonstrates the viability and potential of using short peptides to mimic the minimal functional site of natural enzymes.