A novel mechanism for oxidative cleavage of prolyl peptides induced by the hydroxyl radical

Abstract

Mechanism for the oxidative cleavage of proline-containing peptides induced by the hydroxyl radical ( •OH) has been studied. Accompanying the oxidation of prolyl peptides, we discovered the formation of significant amounts of γ-aminobutyric acid (GABA) in the acid hydrolysates of the oxidized peptides. GABA was assumed to be derived from the 2-pyrrolidone compound and, in addition, its generation led to the assumption that prolyl peptides were mainly cleaved at the proline residues by •OH, accompanied by the oxidative modification of proline by itself. Hence, in order to confirm this prediction, we undertook the reaction of proline with •OH using proline analogue (Z-proline) and isolated the 2-pyrrolidone compound as the major product. We proposed a novel mechanism for formation of the 2-pyrrolidone compound induced by •OH, which has been established for the first time in the oxidative cleavage of prolyl peptides.