Selective protein oxidation through reactive oxygen species: Catalysis by cysteine

BIOT 137

Christian Schoneich, schoneic@ku.edu, Department of Pharmaceutical Chemistry, University of Kansas, 2095 Constant Avenue, 104 McCollum Labs, Lawrence, KS 66047
Oxidation represents a major degradation pathway for protein formulations in solutions and solids. The parameters controlling protein oxidation are not as well understood as it would be desirable for the rational design of oxidation-resistant formulations. An important feature of the reaction of a protein with a reactive oxygen species/free radical is that the initial site of attack may not necessarily represent the final location of an oxidation site. In this presentation, we will demonstrate the potential of Cys residues to serve as a point of primary attack with intermediary Cys thiyl radicals subsequently attacking other amino acids within the protein sequence. Thiyl radicals can either involve in reversible hydrogen transfer reactions, electron transfer, or in addition reactions to aromatic amino acid residues. Experimental evidence will be provided for each of these pathways.