Abstract
The active site of the enzyme galactose oxidase (GOase) contains square‐pyramidal monocopper site, one of whose ligands is a tyrosinate side‐chain that is oxidized to an unusually stable radical in the active enzyme. The structure of this non‐innocent tyrosinate is unique in two ways. First, the tyrosine ring is crosslinked to a neighboring cysteine residue, affording an orthoalkylsulfanyl‐substituted phenoxide ligand. Second, this assembly is protected by a π–π interaction to a tryptophan indole group. We describe here a series of compounds designed to model various aspects of the structure of this unusual cofactor. Our studies have shown that the thermodynamic stability of the GOase radical can be attributed almost exclusively to its thioether substituent, that the π–π interaction contributes little to this stability, and that the assignment of the optical spectrum of the GOase radical is more complex than had been previously suggested. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:494–500, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10091