Identification and characterization of protein cross-links induced by oxidative reactions

ABSTRACT

Introduction: Protein cross-links are common in biological systems and are generated both deliberately as a part of normal metabolism and also accidently as a result of exposure to external factors such as oxidation and glycation stresses. These cross-links can be both positive and negative for biological function, with high levels of inappropriate cross-links being associated with multiple human pathologies, as well as loss of protein structure and function in the food, agricultural, and pharmaceutical fields.

Areas covered: This review covers recent advances in the detection and identification of protein cross-links arising from oxidation reactions, mediated by both radicals and two-electron oxidants. Information on both enzymatic and nonenzymatic cross-linking is reviewed, both where this is intentional, as part of normal metabolism, and accidental and a potential cause of disease.

Expert commentary: The advantages and drawbacks of various methods available for the detection, identification, and quantification of these species are discussed, as well as some of the mechanisms and processes known to give rise to these species.

KEYWORDS:

• Protein oxidation
• cross-linking
• mass spectrometry

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

The authors are grateful for financial support of their studies by the Novo Nordisk Foundation (grant: NNF13OC0004294), the Danish Council for Independent Research | Natural Sciences (grants: DFF-7014-00047 and 11-106246), and the Velux Foundation. The Danish Research Foundation, Nordic Bioscience A/S and Technical University of Denmark are acknowledged for a cofunded PhD scholarship to MM.