Generation and propagation of radical reactions on proteins

Abstract

The oxidation of proteins by free radicals is thought to play a major role in many oxidative processes within cells and is implicated in a number of human diseases as well as ageing. This review summarises information on the formation of radicals on peptides and proteins and how radical damage may be propagated and transferred within protein structures. The emphasis of this article is primarily on the deleterious actions of radicals generated on proteins, and their mechanisms of action, rather than on enzymatic systems where radicals are deliberately formed as transient intermediates. The final section of this review examines the control of protein oxidation and how such damage might be limited by antioxidants.

Oxidation of proteins: Basic principles and perspectives for blood proteomics

“…The gist of this section is not to give a comprehensive and detailed overview of protein oxidation mechanisms; this has been done elsewhere [39][40][41][42][43][44]. It is rather to provide an overview of protein oxidation products in terms of diversity and chemical specificity in order to highlight the possible analytical workflows and current challenges in redox proteomics.…”

“…In the presence of oxygen, a hydroxyl group can be added to this carbon-centred radical. The hydroxylated a-carbon can then undergo peptide backbone cleavage at the N-C bond through the a-amidation pathway, which leaves an amide at the C-terminal side of the N-terminal part of the protein, and a a-keto-acyl residue at the N-terminal side of the C-terminal part of the protein [40,42,[46][47][48].…”

“…2C [40,42,49]: the release of the side chain as a carbonyl compound leaves a radical on the a-carbon, which is then prone to backbone cleavage through mechanisms similar to that of the diamide or a-amidation pathways.…”

“…3 [13,42,50]. They can also result from backbone cleavage through the aamidation pathway or b-scission.…”

Characterization of O2 (1Δg)-derived oxidation products of tryptophan: A combination of tandem mass spectrometry analyses and isotopic labeling studies

“…This is the case for the products generated by the action of O 2 ( 1 ⌬ g ) and other oxidizing conditions, such as the addition of a hydroxyl radical to the pyrrole moiety, followed by loss of water and addition of superoxide radical or molecular oxygen [23,24]. In a previous work, we have shown that tryptophan oxidation by O 2 ( 1 ⌬ g ) gives rise to cis-and transtryptophan hydroperoxides (WOOH), which can further decompose into the corresponding isomeric alcohols (WOH) and FMK (Scheme 1) [25].…”