dityrosine

Dityrosine is a covalent crosslink formed when two tyrosine residues in proteins are linked by an oxidative coupling of their phenolic rings, creating a dityrosine bond. It most commonly arises through the oxidation of tyrosine side chains to tyrosyl radicals, which then couple under the influence of reactive oxygen and nitrogen species such as peroxynitrite, hydroxyl radicals, or ultraviolet light. The result is a stable, non-reducible crosslink that can occur in proteins and peptide assemblies.

Dityrosine crosslinks occur in a range of biological contexts, particularly in extracellular matrix proteins like collagen and elastin, as well as in lens proteins and other oxidatively modified proteins at sites of stress. Formation of these crosslinks can alter mechanical properties by increasing crosslink density, reducing solubility, and decreasing proteolytic susceptibility, contributing to aging-related stiffening and tissue degeneration. Dityrosine formation is associated with various diseases where oxidative stress is elevated, including neurodegenerative disorders, cataracts, and atherosclerosis.

In research, dityrosine is used as a biomarker of oxidative protein damage. It is intrinsically fluorescent, typically excited near 320–360 nm with emission around 420–430 nm, which enables spectroscopic detection in proteins and tissues. Additional methods for detection and quantification include mass spectrometry and immunoassays that use anti-dityrosine antibodies. Measuring dityrosine levels helps assess the extent of oxidative crosslinking in biological samples.