Combinatorial approaches to functional models for galactose oxidase.
The copper enzyme galactose oxidase (GOase, EC 1.1.3.9) catalyses the oxidation of D-galactose and other primary alcohols in air to the corresponding aldehydes and hydrogen peroxide. The current mechanistic hypothesis for this two-electron redox reaction involves a Cu(I)/Cu(II) couple and the reversible oxidation of a ligating phenolate (tyrosine residue of the Tyr272-Cys228 conjugate) to a phenoxyl radical. Our approaches to functional models for galactose oxidase comprise both the use of low-molecular-weight copper complexes of a Schiff-base and sulfonamide ligands, and the synthesis/screening of combinatorial libraries. With regard to the latter, we have synthesized (by the IRORI-directed synthesis approach) peptide libraries carrying either His or the redox-active amino acids Tyr, mod-Cys (a model for the Tyr272-Cys228 conjugate) or TOAC (a TEMPO-derived alpha-amino acid) at four variable positions. After incubation with copper ions, the catalytically active library members were identified by specially designed screening methods.
Berkessel
Albrecht
A
Institut für Organische Chemie der Universität zu Köln, Greinstrasse 4, D-50939 Köln, Germany. berkessel@uni-koeln.se
Dousset
Magali
M
Bulat
Stephan
S
Glaubitz
Katja
K
D032701:Biomimetics; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003300:Copper / Q000737:chemistry*; D005692:Galactose Oxidase / Q000737:chemistry*; D008956:Models, Chemical; D019151:Peptide Library
D019151:Peptide Library; D003300:Copper; D005692:Galactose Oxidase