Reactive species formed on proteins exposed to singlet oxygen

Abstract

Singlet oxygen (¹O₂) is believed to be generated in biological systems by a range of endogenous processes (e.g. enzymatic and chemical reactions) and exogenous stimuli (e.g. UV or visible light in the presence of a sensitiser). Kinetic data is consistent with proteins being a major target for ¹O₂, with damage occurring preferentially at Trp, His, Tyr, Met, and Cys side-chains. Reaction with each of these residues gives rise to further reactive species. In the case of Trp and Tyr, initial poorly characterised endoperoxides are believed to undergo ring-opening reactions to give hydroperoxides, which can be reduced to the corresponding alcohols; other products arising from radical intermediates can also be generated, particularly in the presence of UV light and metal ions. With His side-chains, poorly characterised peroxides are also formed. Reaction with Met and Cys has been proposed to occur via zwitterionic peroxy intermediates. Peroxides are also generated on isolated proteins, and protein within intact cells, via¹O₂-mediated reactions. The peroxides formed on Trp, Tyr, and His peptides, as well as on proteins, have been shown to induce damage to other targets, with molecular oxidation of thiol residues an important reaction. This can result in the inactivation of cellular enzymes and the oxidation of other biological targets. Protein cross-linking and aggregation can also be induced by reactive species formed on photo-oxidised proteins, though the nature of the species that participate in such reactions is poorly understood. These secondary reactions, and particularly those involving hydroperoxides, may play a key role in the induction of secondary damage (bystander effects) in systems subject to photo-oxidation.