# Stability and Pseudocatecholase Activity of Artificial Bis-Histidyl Copper Peptides

## TL;DR

This paper designs artificial peptides that mimic metalloenzymes and efficiently catalyze catechol oxidation reactions.

## Contribution

The study introduces novel bis-histidyl peptides with pseudocatecholase activity and structural insights for bioinspired metalloenzyme development.

## Key findings

- Bis-histidyl peptides show efficient catalytic activity for catechol oxidation.
- Peptide coordination with Cu(II) and Cu(I) was analyzed using multiple spectroscopic techniques.
- Structural constraints around the active site are crucial for catalytic function.

## Abstract

In this paper, 4-methylcatechol
(4-MC) and L/D-Dopa are
selected
as target substrates for de novo protein design,
serving as a proof-of-concept system for evaluating the catalytic
activity of metal coordination sites. We report two novel water-soluble
bis-histidyl peptides that exhibit catalytic activity, where structural
constraints around the active site would play a pivotal role in metalloenzyme
development. The particular tandem His–His motif in the peptides
and favorable E
0′ enable them to
catalyze catechol oxidation reactions efficiently. The coordination
behavior of the peptides with Cu­(II) and Cu­(I) ions is thoroughly
investigated using a combination of analytical techniques, including
potentiometric titration and fluorescence, ultraviolet–visible
(UV–vis), and circular dichroism (CD) spectroscopies. The insights
gained into the catalytic binding site and associated pseudocatecholase
activity of these peptides contribute to the development of copper-based
bioinspired artificial metalloenzymes.