Cyclodecapeptides to mimic the radical site of tyrosyl‐containing proteins

Tyrosyl radicals are involved in many biologically important processes. The development of model compounds to mimic radical enzyme active sites, such as galactose oxidase (GO), has widely contributed to an enhanced understanding of their spectral properties, structural attributes and even reactivity. An emerging approach towards the synthesis of such active site mimetics is the use of peptidic ligands. The potential of cyclodecapeptides to bear phenoxyl radicals has been evaluated through three compounds. LH42+ is a cyclodecapetide containing two histidine residues (mimicking His496 and His581 of GO) and two tyrosine residues (mimicking Tyr495 and the Tyr272• radical of GO). LtBuH42+ and LOMeH42+ incorporate 2,4,6‐protected phenols in place of each tyrosine in LH42+. The deprotonation constants of each peptide determined by potentiometric titrations showed that there are some interactions between the acido‐basic residues. Cyclic voltammetric studies revealed that only the peptides incorporating 2,4,6‐protected phenolates exhibit reversible redox couples and are thus precursors of radicals stable enough to persist in solution. These studies also showed LOMe2− to possess the lower oxidation potential, indicating that this peptide, in its radical form, is the most stabilized. The electrochemically generated radical species have been characterized by EPR spectroscopy. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.